Investigation of colistin utilization in the treatment of multidrug-resistant gram-negative nosocomial bloodstream infections in children and literature review.

This retrospective study aimed to assess the effectiveness and safety of colistin used in combination therapy for treating nosocomial bloodstream infections caused by multi-drug resistant gram-negative pathogens in pediatric patients. Patients aged between 1 month and 18 years consecutively hospitalized with healthcare-associated bloodstream infections necessitating the administration of intravenous colistin at Dr. Sami Ulus Training and Research Hospital between January 2015 and January 2020 were included in the study. Patient-specific detailed clinical information, prognoses, and laboratory findings on days 1, 3, and 7 of colistin treatment were obtained from medical records. The study included 45 pediatric patients receiving intravenous colistin; 26 (57.8%) were male and 19 (42.2%) were female, with a median age of 18 months. While the clinical response was observed at 82.2% and microbiological response at 91.1% with colistin treatment, two patients (4.4%) discontinued treatment due to side effects without assessing treatment response. The most common adverse effect associated with the use of colistin was nephrotoxicity, which occurred in eight patients (17.8%). Among these patients, only one had pre-existing chronic kidney failure.    Conclusion: Colistin used in combination therapy may be effective and safe for treating nosocomial infections caused by multi-drug resistant gram-negative bacteria in pediatric patients, who often have high mortality rates and limited treatment options. What is Known: • Colistin is an antibacterial agent used in the treatment of infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) and is associated with significant adverse effects such as nephrotoxicity. • The increasing prevalence of hospital-acquired infections has led to the expanded use of colistin in clinical practice. What is New: • The study demonstrates a high clinical and microbiological response rate to combination therapy with colistin in the treatment of infections caused by MDR-GNB. • The study highlights the importance of monitoring nephrotoxicity in pediatric patients receiving colistin, showing that these effects can be reversible after treatment cessation.

Pathogens in Pediatric Septic Arthritis: A Multi-Center Study in Turkiye (PEDSART Study).

OBJECTIVES: Septic arthritis (SA) is a serious bacterial infection that must be treated efficiently and timely. The large number of culture-negative cases makes local epidemiological data important. Accordingly, this study aimed to evaluate the etiology, clinical characteristics, and therapeutic approach of SA in children in Turkiye, emphasizing the role of real-time polymerase chain reaction (PCR) techniques in the diagnosis. METHODS: In this multi-center, prospective study, children hospitalized due to SA between February 2018 and July 2020 in 23 hospitals in 14 cities in Turkiye were included. Clinical, demographic, laboratory, and radiological findings were assessed, and real-time PCR was performed using synovial fluid samples. RESULTS: Seventy-five children aged between 3 and 204 months diagnosed with acute SA were enrolled. Joint pain was the main complaint at admission, and the most commonly involved joints were the knees in 58 patients (77.4%). The combination of synovial fluid culture and real-time PCR detected causative bacteria in 33 patients (44%). In 14 (18.7%) patients, the etiological agent was demonstrated using only PCR. The most commonly isolated etiologic agent was Staphylococcus aureus, which was detected in 22 (29.3%) patients, while Streptococcus pyogenes was found in 4 (5.3%) patients and Kingella kingae in 3 (4%) patients. Streptococcus pyogenes and Kingella kingae were detected using only PCR. Most patients (81.3%) received combination therapy with multiple agents, and the most commonly used combination was glycopeptides plus third-generation cephalosporin. CONCLUSIONS: Staphylococcus aureus is the main pathogen in pediatric SA, and with the use of advanced diagnostic approaches, such as real-time PCR, the chance of diagnosis increases, especially in cases due to Kingella kingae and Streptococcus pyogenes.

Tuberculosis contact-tracing results in childhood: a retrospective study in a tertiary-care children's hospital in Turkey.

BACKGROUND: Smear-positive adults with tuberculosis are the main source of childhood tuberculosis. The evaluation of children exposed to tuberculosis and determination of the disease stages are the cornerstones of managing childhood tuberculosis. AIM: To determine the frequency of tuberculous contact, latent tuberculosis infection and tuberculosis disease in children who were in contact with smear-positive adults. METHODS: This is a single-centre, retrospective study. The medical records of children exposed to tuberculosis (<18 years old) between 2014 and 2018 were investigated. After diagnosing the index cases, the children were referred to the hospital. To identify the children in contact with adults with tuberculosis, a careful medical history, demographic features and physical examination, tuberculin skin test, postero-anterior and lateral chest radiographs, and, if necessary, chest computed tomography and microbiological tests were undertaken. The children's final diagnosis, treatment regimens and follow-up were documented. The sensitivity, specificity and positive and negative predictive values, tuberculin skin test and chest radiograph imaging were assessed and compared with computed tomography results. RESULTS: A total of 150 paediatric patients were exposed to 88 index cases. These were fathers in 29.3% of cases and mothers in 10% of cases. Of the children, 131 (87.3%) were asymptomatic, and physical examination was normal in all children, apart from one who had respiratory symptoms. The tuberculin skin test results were positive in 60 (43%) patients and chest radiograph was abnormal in 100 (66%) children. Findings were consistent with tuberculosis in 34 (40%) of the 84 patients who underwent computed tomography. Fifty (38.5%) of the remaining children were defined as having been in contact with a case of tuberculosis, 41 (31.5%) had latent tuberculous infection and 39 (30%) had tuberculosis disease. CONCLUSION: Pulmonary tuberculosis is asymptomatic in most children but with meticulous use of computed tomography it can be detected in asymptomatic children who have had close contact with tuberculosis.Abbreviation: AFB: acid-fast bacilli; AUC: area under the curve; BCG: bacillus Calmette-Guérin; CI: confidence interval; CT: computed tomography; CXR: chest radiograph; HIV: human immunodeficiency virus; ICD-10: International Classification of Diseases 10; LTBI: latent tuberculosis infection; MDR-TB: multi-drug-resistant tuberculosis; NPV: negative predictive value; PCR: polymerase chain reaction; PPV: positive predictive value; ROC: receiver operating characteristics; SD: standard deviation; TB: tuberculosis; TST: tuberculin skin test; XDR-TB: extensively drug-resistant tuberculosis.

Community-acquired S. aureus infection in childhood: a multi-center study.

BACKGROUND: The prevalence of community-acquired methicillin-resistant S. aureus (CA-MRSA) has been increasing worldwide. We aimed to investigate the prevalence of MRSA in community-acquired S. aureus infections, the risk factors for CA-MRSA infection and the clinical features of CA-MRSA. METHODS: A multi-center study with prospective and retrospective sections was conducted. Patients ≥ 3 months old and ≤18 years of age who were diagnosed with community-acquired S. aureus infections were included in this study and the patients` information were reviewed from the medical and microbiological database of the hospital. A standard question form about living conditions and exposure risk factors was administered to the parents of patients. The CA-MRSA infections were compared with the methicillin-susceptible S. aureus (CAMSSA) infections in terms of the queried risk factors and clinical variables. RESULTS: We identified 334 pediatric patients with S. aureus infection, 58 (17.4%) had an infection with CAMRSA. The refugee rate was higher in the CA-MRSA group. There was no significant difference regarding the exposure risk. The treatment modalities and outcomes were similar. CONCLUSIONS: The study was not able to show reliable clinical variables or epidemiological risk factors except for being a refugee for CA-MRSA infections. Empirical antibiotic treatment should therefore be determined according to the local CA-MRSA prevalence in patients presenting with a possible staphylococcus infection.

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.

Distinguishing orbital cellulitis from preseptal cellulitis in children.

PURPOSE: We aimed to evaluate clinical and laboratory characteristics of children with preseptal cellulitis (PC) and orbital cellulitis (OC) and also to determine whether clinical and/or laboratory parameters could be used to distinguish OC from PC. METHODS: The medical records of pediatric patients (aged between 1 month and 18 years) with PC and OC who had been hospitalized at our center from January 2008 to December 2020 were retrospectively reviewed. Multivariable regression analysis was performed to identify possible parameters useful in differentiating between PC and OC. RESULTS: A total of 375 patients [202 (53.9%) boys], of whom 35 (9.3%) had OC, were evaluated. Median age was 44 (range, 1-192) months. Compared to those with PC, patients with OC were older (p = 0.001), had fever, upper respiratory tract infection (URTI) symptoms, and sinusitis more frequently, and demonstrated prolonged symptom and hospitalization times (p Ë‚ 0.001 for all). Significant differences between groups were observed for numerous laboratory parameters; however, multivariable regression analysis revealed that only C-reactive protein (CRP) and platelet count could be used to predict OC among the laboratory findings. Taken together, factors independently associated with OC diagnosis were proptosis, ophthalmoplegia, age (>35 months), CRP level (˃116.5 mg/L), and platelet count (˃420.5 × 103/mm3). CONCLUSION: In addition to showing previously known properties of OC versus PC, our study demonstrated that combined demographic, clinical and laboratory factors such as being aged above 35 months, having a CRP level of ˃116.5 mg/L, and platelet count of ˃ 420.5 × 103/mm3 could be used to distinguish OC from PC.

Clinical and radiologic manifestations of Mycoplasma pneumoniae infection in children.

BACKGROUND: Mycoplasma pneumoniae (MP) is one of the most important etiological agents of communityacquired pneumonia in children. METHODS: The medical records of children with an MP infection between 2008 and 2015 were reviewed for their clinical, laboratory radiological features. RESULTS: This study included 244 patients (male 57.4%) with a median age of 80.5 months (IQR, 46.5-120 months). A total of 78 (32%) patients were < 5 years old, and 166 (68%) were ≥ 5 years old. The most common complaints before admission to the hospital were cough (84.8%), fever (57.4%), and weakness (18.9%). In the < 5 years old age group, oxygen saturation was lower, and tachypnea was more common than in the ≥ 5 years old age group (p=0.02 and p=0.05, respectively). Similarly, the physical findings such as the prolonged expiration, presence of retractions, and rhonchi were more frequent in the < 5 years old age group (p=0.001, p=0.000, p=0.02, respectively). Extrapulmonary manifestations were present in 45 (18.4%) patients, and skin involvement was the most common one (7.7%). Two hundred-thirty-eight (97.5%) patients had chest radiographs, and 45 (18.4%) had normal radiography. The most common radiological involvement was peribronchial infiltration (n=70, 28.7%). Of the patients, 147 (60.2%) were hospitalized, and 97 (39.7%) were followed up as outpatients. It was determined that 156 (63.9%) patients had commenced macrolide empirically, and 61 (25%) patients were treated with positive serology results. CONCLUSIONS: The prolonged fever, cough and expiration time, wheezing and rhonchi in younger children, and segmental-lober consolidation in chest radiography could be clues for MP infection. Further studies in different age groups can facilitate an understanding of MP infection`s epidemic characteristics and clinical features that will provide early diagnosis and appropriate treatment.

Is There a Role for Laboratory Parameters in Predicting Coronary Artery Involvement in Kawasaki Disease?

BACKGROUND: Kawasaki disease (KD) may cause cardiac and coronary complications. Since definite markers to accurately predict coronary involvement is not present, we aimed to analyze the role of hematological indices [neutrophil-to lymphocyte ratio (NLR), platelet-to lymphocyte ratio (PLR), lymphocyte-to monocyte ratio (LMR), and mean platelet volume (MPV)-to lymphocyte ratio (MPVLR)], prognostic nutritional index (PNI) and systemic immune-inflammation index (SII) in predicting coronary involvement of KD. Patients The medical records of 134 KD patients admitted between January 2008 and December 2019 were investigated. Also, 268 age-matched healthy controls (HCs) were included in the study. METHODS: KD patients were divided into two groups: KD with coronary artery lesions (KD-CALs) and KD without CALs. Logistic regression analysis was performed to determine parameters that may predict coronary involvement in children with KD. RESULTS: Among KD patients, 39 (29.1%) had CALs. When compared with HCs, the median levels of WBC, neutrophils, monocytes, eosinophils, platelets, MPV and, the values of NLR, PLR, MPVLR, SII were significantly higher; whereas lymphocyte count, PNI, platelet distribution width (PDW), LMR were markedly lower in the KD group (p˂0.001 for all, except for p=0.010 for eosinophil count). The CALs group's SII, PLR, and PNI values were significantly lower than those without (p=0.030, p=0.032, and p ˂0.001; respectively). Multivariable regression analysis revealed that PNI, SII, and gender (male) were associated with CALs in KD. CONCLUSION: Our analysis revealed that male sex, lower PNI, and lower SII levels were independently associated with CALs in children with KD.

Clinicoepidemiological findings of childhood brucellosis in a tertiary care center in Central Anatolia: with the emphasis of hematological findings.

BACKGROUND: Human brucellosis is one of the most widespread zoonotic diseases that are presented with predominantly hematological manifestations. We aimed to evaluate the hematological findings of childhood brucellosis and to determine the predictive clinical findings and laboratory tests that might be related to hematologic involvement. METHODS: We retrospectively analyzed the medical records of children with brucellosis between 1 January 2005 and 31 December 2018. We compared predictive clinical and physical examination findings and laboratory tests in patients with and without hematological involvement. RESULTS: A total of 212 patients (127 boys (59.9%)) with a mean age of 9.4±4.7 years were evaluated in this study. Blood cultures were performed in 161 (75.9%) patients and Brucella spp were isolated in 70 (43.4%) of them. Ninety-two (43.4%) patients had hematological involvement at least in one series. Anemia was detected in 66 (31.7%) patients, leukopenia in 22 (10.6%) and thrombocytopenia in 10 (4.8%). Four patients (1.9%) had pancytopenia. Age distrubutions of the patients with and without hematological involvement were similar (p=0.6). In patients presented with fever, hepatomegaly and splenomegaly, hematologic involvement was significantly higher (p < 0.05). Hematological involvement was higher in patients who had elevated aspartate aminotransferase and alanine aminotransferase concentrations (p < 0.05). Hematological involvement was higher in patients with positive blood culture (p=0.005). Six patients (2.8%) were treated with intravenous immunoglobulin at 1000 mg/kg/day for two days in addition to anti-brucellosis treatment. CONCLUSIONS: Hematological involvement in brucellosis is a common finding regardless of age, especially in febrile, bacteremic patients and in patients who had hepatosplenomegaly and elevated liver enzymes. Anemia is the most common hematological abnormality.

Bacteremic and Nonbacteremic Brucellosis in Children in Turkey.

INTRODUCTION: Human brucellosis is one of the most common zoonotic infections in the world. The definitive diagnosis of brucellosis is based on cultured Brucella organisms from blood or other tissue samples. We aimed to compare bacteremic and nonbacteremic brucellosis patients with demographical, epidemiological, clinical and laboratory features and determine the predictive factors affecting blood culture positivity. MATERIALS AND METHODS: Children aged 1 month to 18 years who were followed up with the diagnosis of brucellosis between January 2005 and March 2021 were included in this retrospective study. According to the isolation of Brucella melitensis in blood culture, the patients were divided into two groups as bacteremic and nonbacteremic and compared in terms of demographic, clinical and laboratory characteristics. RESULTS: One hundred eighty-nine (116 male, 61.4%) patients diagnosed with brucellosis were included in the study. There were 76 (40.2%) bacteremic and 113 (59.8%) nonbacteremic patients. Bacteremic patients were younger than nonbacteremic patients. Fever, arthralgia, hepatomegaly and splenomegaly were significantly higher in the culture positive group. High levels of C-reactive protein (CRP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were found to be significant in the bacteremic group. CONCLUSION: In our study, history of fever and arthralgia, hepatomegaly and splenomegaly in physical examination and high CRP, ALT and AST levels in the biochemical analysis were important factors determining blood culture positivity.

A Case of Multisystem Inflammatory Syndrome in a 12-Year-old Male After COVID-19 mRNA Vaccine.

The pathophysiology of multisystem inflammatory syndrome (MIS) in children (MIS-C) is unknown. It occurs several weeks after COVID-19 infection or exposure; however, MIS is rarely reported after COVID-19 vaccination, and cases are mostly in adults. Herein, we present a 12-year-old male who had no prior COVID-19 infection or exposure and developed MIS-C after his first dose of COVID-19 mRNA vaccine.

Multisystem inflammatory syndrome in children during severe acute respiratory syndrome coronavirus-2 pandemic in Turkey: A single-centre experience.

AIM: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection may result in a life-threatening hyperinflammatory condition named multisystem inflammatory syndrome in children (MIS-C). We aimed to assess demographics, clinical presentations, laboratory characteristics and treatment outcomes of patients with MIS-C. METHODS: We performed a retrospective study of patients with MIS-C managed between August 2020 and March 2021 at Dr. Sami Ulus Maternity Child Health and Diseases Training and Research Hospital in Turkey. RESULTS: A total of 45 patients (23 male, 51%) with a median age of 8.7 years (interquartile range: 5.6-11.7 years) were enrolled to study. The SARS-CoV-2 serology was positive in 43 (95%) patients. Organ-system involvement included the dermatologic in 41 (91%), cardiovascular in 39 (87%), hematologic in 36 (80%) and gastrointestinal in 36 (80%) patients. Acute anterior uveitis was diagnosed in nine (20%) patients. Two patients presented with clinical findings of deep neck infection such as fever, neck pain, trismus, swelling and induration on the cervical lymph node. One patient presented with Henoch-Schonlein purpura-like eruption. Coronary artery dilatation was detected in five (11%) patients. For treatment of MIS-C, intravenous immunoglobulin was used in 44 (98%) patients, methylprednisolone in 27 (60%) and anakinra in 9 (20%) patients. The median duration of hospitalisation was nine days. All patients recovered. CONCLUSIONS: Children with MIS-C might have variable clinical presentations. Acute anterior uveitis might be a prominent presentation of MIS-C and require ophthalmological examination. It is essential to make patient-based decisions and apply a stepwise approach for the treatment of this life-threatening disease.

Bloodstream infections due to Trichosporon species in paediatric patients: Results from the first national study from Turkey.

BACKGROUND: Invasive Trichosporon infections are rarely seen opportunistic fungal infections in children and mainly affect immunocompromised patients. This multicenter retrospective study has rewieved the characteristics, risk factors, treatment modalities and outcomes of bloodstream infections caused by Trichosporon species in children diagnosed over the past ten years in Turkey. METHODS: The study was performed with the participation of 12 of 55 hospitals invited from Turkey. In each center, the patients with bloodstream infections caused by Trichosporon spp. between January 2010 and December 2020 were retrospectively ascertained and the results were reported to the study coordinator by means of a simple case report. Data were collected on patient demographics, underlying condition(s), treatment of.infections caused by Trichosporon spp, and 7 and 30- day mortality rates. RESULTS: A total of 28 cases with fungemia caused by Trichosporon spp. were included in the study. The most common underlying disease was paediatric cancers (39.3%). T. asahii infections were detected in 78.5 % (n=22) of patients. A various spectrum of antifungal treatment regimens were used including intravenous amphotericin B monotherapy in 35.7%, intravenous amphotericin B and voriconazole combination in 32.1% and intravenous voriconazole monotherapy in 28.6% of the patients. The overall mortality rate was 28.5 %. The mortality rates were 12.5% in the voricanozole, 30% in the amphotericin B and 33.3% in combined voriconazole -amphotericin B arms CONCLUSIONS: Invasive Trichosporon infections with an important impact of patients quality of life are almost related to underlying diseases with an overall mortality rate of 28.5%. Voriconazole was found to be associated with lower mortality rates when compared with other treatment regimens.

Factors associated with acyclovir nephrotoxicity in children: data from 472 pediatric patients from the last 10 years.

Acyclovir may cause acute kidney injury (AKI) due to the accumulation of relatively insoluble acyclovir crystals in renal tubules. The aim of this study was to evaluate risk factors associated with acyclovir-related AKI in children. Between January 2010 and December 2019, pediatric recipients of intravenous (IV) acyclovir were evaluated retrospectively. There were a total of 472 patients [249 (52.7%) boys] of which 32 (6.8%) had AKI [15 (46.8%) boys]. Patients with AKI had greater mean age, baseline creatinine level, and duration of treatment compared to patients without AKI (p<0.001). In the AKI group, concomitant nephrotoxic drug use was more frequent (p=0.032), and the percentage of patients treated with 1500 mg/m2/day dosage was higher (p<0.001). AKI was diagnosed at a mean of 4.3 ± 2.5 days after acyclovir initiation and creatinine levels returned to normal at a mean of 7.3 ± 3.6 days after AKI diagnosis. Only eight patients (25%) had vomiting which led to suspicion of AKI. Being older than 100.5 months (HR: 4.501, 95% CI: 1.802-11.241; p=0.001), use of 1500 mg/m2/day acyclovir (HR: 9.536, 95% CI: 2.157-42.158; p=0.003) and use of concomitant nephrotoxic drugs (HR: 5.043, 95% CI: 2.289-11.109; p<0.001) were the factors that independently increased the likelihood of nephrotoxicity.Conclusion: Most patients were asymptomatic when they were diagnosed with AKI. Clinicians should be aware of AKI risk in pediatric patients with risk factors (age >100.5 months, 1500 mg/m2/day dosage, concomitant use of nephrotoxic drugs). Acyclovir dosing should be evaluated in prospective, multicenter studies in order to identify the lowest possible therapeutic doses that do not increase AKI risk. What is Known: • Although acyclovir is mostly well tolerated, nephrotoxicity may be seen due to the accumulation of acyclovir crystals in renal tubules. • Older age, obesity, and concomitant use of other nephrotoxic drugs are reported to be risk factors for acyclovir-induced AKI in children. What is New: • In this study, pediatric patients with acyclovir-induced AKI were older, received treatment longer, received concomitant nephrotoxic drugs more commonly, and had higher acyclovir dosage and baseline creatinine levels compared to those without AKI. • Being older than 100.5 months of age, use of 1500 mg/m2/day dosage and use of nephrotoxic drugs concomitantly appear to be the prominent risk factors for AKI development in children treated with acyclovir.