Pan drug-resistant Acinetobacter baumannii causing nosocomial infections among burnt children.

Background: Nosocomial infection caused by Acinetobacter baumannii has emerged as a world-wide serious problem in the emergence of multidrug-resistant (MDR). Infections caused by antibiotic-resistant strains of A. baumannii cannot be completely eliminated among the infected patients. This study aimed to monitor antibiotic resistance among A. baumannii strains isolated from burnt children. Methods: After performing biochemical identification tests on 115 isolates, 62 were detected as A. baumannii . Minimum inhibitory concentration (MIC) was used to test susceptibility to colistin, and disk agar diffusion was used for the susceptibility of the isolates to the antibiotics Ciprofloxacin, Amikacin, Gentamicin, Cefepime, Meropenem, Imipenem, Ceftazidime, Levofloxacin and Piperacillin/Tazobactam. Bacterial species were isolated and identified as multidrug-resistant (MDR), extensively drug-resistant (XDR) and pan drug-resistant (PDR), based on the susceptibility patterns to elected antibiotics, deputing different classes of antimicrobial. Results: The antibiotic susceptibility pattern out of a total of 62 bacterial strains used in this study. Thirty-six (58%) strains were categorized as MDR, 17 (27.5%) as XDR, and nine (14.5%) as PDR. Conclusion: To reduce the threat of antimicrobial resistance, MDR, XDR and PDR A. baumannii strains must be evaluated by all clinical microbiology laboratories.

Cernunnos defect in an Iranian patient with T- B+ NK+ severe combined immunodeficiency: A case report and review of the literature.

BACKGROUND: Defective Cernunnos gene in nonhomologous end-joining (NHEJ) pathway of the DNA repair is responsible for radiosensitive severe combined immunodeficiency (SCID). Herein, presented a new patient with Cernunnos deficiency and summarized the clinical, immunological, and molecular features of reported patients in the literature. CASE: The patient was a 6-month-old female born to consanguineous parents. She presented with long-lasting fever, diarrhea, poor feeding, and restlessness. She had suffered from recurrent fever of unknown origin and multiple episodes of oral candidiasis. In the physical examination, microcephaly, failure to thrive, oral candidiasis, pustular rash on fingers, and perianal ulcers, but no dysmorphic feature were observed. The immunologic workup revealed lymphopenia, neutropenia, normocytic anemia, low T- but normal B- and natural killer (NK)- cells, low immunoglobulin (Ig)G, and normal IgA, IgM, and IgE. The T-cell receptor excision circle (TREC) was low and the lymphocyte transformation test (LTT) was abnormal to mitogens and antigens. She was diagnosed with T- B+ NK+ SCID and improved by intravenous immunoglobulin along with antimicrobials. A homozygous splice site variant, c.390 + 1G > T, at the intron 3 of the NHEJ1, was identified and the diagnosis of Cernunnos deficiency was established. However, while a candidate for hematopoietic stem cell transplantation, she developed sepsis and died at 11 months of age. CONCLUSIONS: Cernunnos deficiency should be considered as a differential diagnosis in patients with microcephaly, growth retardation, recurrent infections, T-cell defects, and hypogammaglobulinemia. The normal B-cell level in the index patient is an unexpected finding in Cernunnos deficiency which requires further evaluation.

Fibrosing mediastinitis in a child with Mendelian susceptibility to mycobacterial disease possibly due to Bacillus Calmette-Guérin.

BACKGROUND: Mendelian susceptibility to mycobacterial disease (MSMD) is an uncommon disorder with increased susceptibility to less virulent mycobacteria including bacillus Calmette-Guérin (BCG). Fibrosing mediastinitis (FM) is also a rare condition defined by excessive fibrotic reactions in the mediastinum. So far, some infectious organisms and autoimmune diseases have been introduced as possible etiologies of FM. However, no study has ever discussed the possible association of BCG infection and FM. CASE PRESENTATION: In this study, we report a 3-year-old female presenting with persistent fever, weakness, and bloody diarrhea in addition to mediastinal lymphadenopathy, hepatosplenomegaly, and pleural and pericardial effusion. Further examinations established a diagnosis of MSMD based on her clinical condition, immunologic data, positive tests for mycobacterial species, positive family history, and genetic study (IL12RB1 gene, c.G1193C, p.W398S). A year and a half later, she was referred with submandibular lymphadenitis and underwent immunologic work-up which revealed high inflammatory indices, a slight reduction in numbers of CD3 + and CD4 + cells as well as elevated CD16/56 + cell count and hyperimmunoglobulinemia. Purified protein derivative (PPD), QuantiFERON, and gastric washing test were all negative. Her chest computed tomography (CT) scan revealed suspicious para-aortic soft tissue and her echocardiography was indicative of strictures in superior vena cava and pulmonary veins. She further underwent chest CT angiography which confirmed FM development. Meanwhile, she has been treated with anti-mycobacterial agents and subcutaneous IFN-γ. CONCLUSION: In summary, we described a novel case of MSMD in a child presenting with granulomatous FM possibly following BCG infection. This is the first report introducing aberrant BCG infection as the underlying cause of FM. This result could assist physicians in identifying early-onset FM in suspicious cases with MSMD. However, more studies are required to support this matter.

Novel PGM3 mutation in two siblings with combined immunodeficiency and childhood bullous pemphigoid: a case report and review of the literature.

BACKGROUND: Bullous pemphigoid is the most common autoimmune subepidermal blistering disorder with a low incidence in childhood. Combined immunodeficiencies (CIDs) are a group of monogenic inborn errors of immunity (IEIs) characterized by T- and B-cell dysfunction leading to recurrent infections, lymphoproliferation, predisposition to malignancy, and autoimmunity. Here, we report two Afghan siblings with a diagnosis of CID and extremely rare manifestation of diffuse bullous pemphigoid skin lesions. CASE PRESENTATION: The older sibling (patient 1) was a 32-month-old male with facial dysmorphism, protracted diarrhea, failure to thrive, recurrent oral candidiasis, recurrent otitis media with tympanic membrane perforation, who had been previously diagnosed with CID. While he was under treatment with intravenous immunoglobulin (IVIg), he developed extensive blistering lesions, which were diagnosed as childhood bullous pemphigoid. Methylprednisolone and azathioprine were added to the regimen, which resulted in a remarkable improvement of the skin lesions and also the feeding condition. However,2 weeks later, he was re-admitted to the intensive care unit (ICU) and eventually died due to fulminant sepsis. Later, his 12-month-old sister (patient 2) with similar facial dysmorphism and a history of developmental delay, food allergy, recurrent oral candidiasis, and respiratory tract infections also developed blistering skin lesions. She was under treatment for occasional eczematous lesions, and had been receiving IVIg for 3 months due to low levels of immunoglobulins. Further immunologic workup showed an underlying CID and thus treatment with IVIg continued, gradually improving her clinical condition. The genetic study of both siblings revealed a novel homozygous mutation in exon 7 of the PGM3 gene, c.845 T > C (p.Val282Ala). CONCLUSIONS: Dermatologic disorders may be the presenting sign in patients with CID and mutated PGM3. This case report further extends the spectrum of skin manifestations that could be observed in PGM3 deficiency and emphasizes the importance of considering CIDs during the assessment of skin disorders, particularly if they are extensive, recurrent, refractory to treatment, and/or associated with other signs of IEIs.

Candidemia in pediatric burn patients: Risk factors and outcomes in a retrospective cohort study.

BACKGROUND AND PURPOSE: Despite advances in burn care and management, infections are still a major contributor to morbidity and mortality rates in patients with burn injuries. Regarding this, the present study was conducted to investigate the prevalence and importance of candidemia in pediatric burn patients. MATERIALS AND METHODS: Blood samples were collected from the patients and cultured in an automated blood culture system. Candida species were identified using specific culture media. The relationship between candidemia and possible risk factors was evaluated and compared to a control group. RESULTS: A total of 71 patients with the mean age of 4.52±3.63 years were included in the study. Blood cultures showed candidemia in 19 (27%) patients. Based on the results, C. albicans was the most common fungus among patients with and without candidemia. The results of statistical analysis also showed that candidemia was significantly correlated with total body surface area (TBSA), mechanical ventilation, duration of total parenteral nutrition, length of intensive care unit (ICU) stay, presence of neutropenia, and R-Baux score (all P≤0.001). In this regard, TBSA, length of ICU stay, R-Baux score, and Candida score were identified as the determinant factors for mortality due to candidemia. CONCLUSION: Candidemia increases the mortality and morbidity rates associated with burn injuries. Prompt diagnostic and prevention measures can reduce the unfortunate outcomes via controlling the possible risk factors.

Survey of efficacy of pediatric appendicitis score in Iranian patients less than 18 years old referred to the emergency department.

INTRODUCTION: Abdominal pain, in particular appendicitis, is a common cause of emergency department visits in children. Therefore, early diagnosis is very important. There are different scoring systems for the diagnosis of appendicitis. This study is the first study to evaluate the performance and accuracy of pediatric appendicitis score (PAS) in Iranian children with abdominal pain in emergency departments. METHODS: This is a cross-sectional study of children under 18 years with suspected appendicitis who were referred to the emergency medicine department of hospitals affiliated to SBMU during 2015. Acute appendicitis was determined according to pathological findings, and final PAS scores were calculated for all children. With statistical analysis, comparison between two groups was calculated and the diagnostic accuracy of PAS score was estimated. RESULTS: 88 children with mean age of 10.5 ± 3 were studied. According to clinical examination 58 of the children were suspected to have acute appendicitis and 30 others were healthy. In current study, the diagnostic accuracy and precision of PAS at cutoff of 5.5 in patients younger than 18 years admitted to the emergency department with suspected acute appendicitis was 91% and 92%, respectively. Sensitivity, specificity, positive predictive value, and negative predictive value were 93.88%, 86.21% and 92%, 89.29%, respectively. CONCLUSIONS: The results of current study showed that PAS has high diagnostic predictive value for the diagnosis of acute appendicitis in children under 18 years and due to the advantages listed for this score, its use is recommended for children in emergencies.

Severe Combined Immunodeficiency: A Case Series and Review from a Tertiary Pediatric Hospital.

Severe combined immunodeficiency syndrome (SCID) is a life-threatening condition leading to early infant death as a result of severe infection, due to impaired cellular and humoral immune systems. Various forms of SCID are classified based on the presence or absence of T cells, B cells and natural killer cells. Patients usually present with recurrent infections and failure to thrive. Definitive treatment is hematopoietic stem cell transplantation. To achieve the best outcome, it should be performed prior to the development of severe infection. In This study, we described 10 patients (6 male and 4 female) with SCID who were admitted to Mofid Children Hospital, Tehran, Iran, from 2006 to 2013. We reviewed patients' clinical manifestation, laboratory data, family history and outcome. The mean age at the time of diagnosis was 131.8 days. One patient had non-consanguineous parents. Seven patients received BCG vaccine before the diagnosis of SCID, three of them showed disseminated BCG infection. One patient presented with invasive pulmonary aspergillosis. Flow cytometric analysis showed T⁻B⁺NK⁻ in three patients, T⁻B⁻NK⁺ in five patients, T⁻B⁻NK⁻ in one patient, and T⁻B⁺NK⁺ in one patient. This study highlights the importance of early diagnosis and patient referral before the occurrence of serious infection.

Vitamin D deficiency and its impact on asthma severity in asthmatic children.

BACKGROUND: Despite obtaining evidences on association between vitamin D and development of lung in fetus, little is known about vitamin D level and its impact on severity of asthma in children. The present study aimed to assess the relationship between the asthma severity and vitamin D deficiency in asthmatic children. METHODS: This case-control study was conducted on 106 individuals including asthmatic (n = 53) and healthy children (n = 53) who referred to Mofid hospital in Tehran in 2013. The level of serum vitamin D in both groups was measured by radioimmunoassay method at the reference lab and was categorized as sufficient (> 30 ng/ml), insufficient (20 to 30 ng/ml), or deficient (< 20 ng/ml). The control status of asthma in patients group was classified as controlled, partially controlled, and uncontrolled. RESULTS: In the groups with and without asthma, the prevalence of vitamin D deficiency was 73.6 and 49.1%, and the prevalence of vitamin D insufficiency was 18.9 and 18.9%, while normal vitamin D level was revealed in 7.5 and 32.1%, respectively with a significant difference (p = 0.005). Using the multivariate logistic regression analysis, the presence of asthma was associated with reduced level of vitamin D (OR = 1.068, 95% CI: 1.027-1.110, P = 0.001). In this context, the risk for asthma in the children with vitamin D deficiency was 6.3 times of those with normal vitamin D level. Although the presence of asthma was strongly associated with reduced level of vitamin D in serum, neither severity of asthma nor control status of asthma were associated with vitamin D deficiency. CONCLUSION: The presence of vitamin D deficiency effectively predict increased risk for childhood asthma; however the severity or control status of this event may not be predicted by confirming vitamin D deficiency.

Serum 25-Hydroxyvitamin D Levels in Pediatric Burn Patients.

BACKGROUND: Previous studies have implicated the important and active role of vitamin D in the immune system. OBJECTIVES: The aim of this study was to evaluate serum levels of 25-hydroxyvitamin D in children with burn injuries. MATERIALS AND METHODS: In this cross-sectional study, 118 patients with various degrees of burn injuries were enrolled. A checklist consisting of demographic data, total body surface area (TBSA) affected by burn, degree of burn, serum level of 25(OH)D, total protein, albumin, electrolytes, and parathyroid hormone was recorded for each patient. RESULTS: Sixty-eight (57.6%) males and 50 (42.4%) females with a mean age of 4.04 years (SD = 3.04) were evaluated. The mean level of 25(OH)D was 14.58 ng/mL (SD = 6.94). Levels of 25(OH)D in four (3.39%) cases were higher than 30 ng/mL, while 95 (81.35%) cases had levels lower than 20 ng/mL, and 19 (16.10%) cases had levels of 21 - 30 ng/mL. The level of 25(OH)D was below recommended levels in 96.61% of cases, while 81.34% had vitamin D deficiency and 16.1% had insufficiency. We found a significant correlation between vitamin 25(OH)D and total protein, albumin, and total and ionized calcium (P < 0.001). There was also a significant negative correlation between 25(OH)D and TBSA affected by burn (P = 0.001). CONCLUSIONS: The levels of 25(OH)D in children suffering from severe burns were low. Supplementation might be useful in patients with very low levels of serum vitamin D.

Colonization of Mycoplasma hominis and Ureaplasma urealyticum in pregnant women and their transmission to offspring.

BACKGROUND AND OBJECTIVES: Mycoplasma hominis and Ureaplasma urealyticum are important opportunistic pathogens that cause urogenital infections and accelerated newborn delivery in pregnant women. Moreover genital mycoplasmas have been implicated in different neonatal diseases such as pneumonia, sepsis and meningitis. This study was conducted to find out the prevalence and transmission rate of these two organisms in pregnant women and their neonates. MATERIALS AND METHODS: Nasotracheal and pharyngeal specimens of 165 newborns hospitalized at Neonatal Intensive Care Unit (NICU) of Rasoul Akram Hospital (during 2010 - 2011) were assessed by PCR to detect M. hominis and U. urealyticum. Moreover, PCR of vaginal specimens from their mothers were obtained to determine the prevalence of these organisms in pregnant women and rate of transmission to their newborns. Data were analyzed using SPSS software. RESULTS: Totally, the results of PCR were positive in 33 newborns (20%). Vaginal colonization among the mothers was found to be 15% (25/165) for U. urealyticum and 15% (25/165) for M. hominis. The transmission rate to their infants was 72% and 60% for U. urealyticum and M. hominis, respectively. CONCLUSION: These data indicate that vertical transmission of mycoplasma and ureaplasma are prevalent in newborns. Since these organisms cause serious infections in neonates, it would be better to perform screening tests in pregnant women before the delivery in order to prevent transmission to neonates and consequent infections and morbidities among them.

Serum immunoglobulin levels in pediatric burn patients.

Infections remain the leading cause of death in burn patients. Immune responses play an important role in patient's defense mechanism against infection and decreasing morbidity and mortality associated with burn. Our goal was to determine serum immunoglobulin levels in pediatric burn patients in order to understand role of humoral immune defense in these patients. During this analytic cross sectional study from January 2011 to February 2012, all patients with burn and younger than 6 years old that were referred to Shahid Motahari burn and reconstruction center were enrolled. Patients had no inhalation injury or sepsis. Immunoglobulin levels were measured once on 3-5 days after burn. The burn size in 12 patients (24%) was less than 30%, in 30 patients (60%) were between 30% and 50% and in the remained 8 patients (16%) were more than 50%. In 45 patients (90%) depth and severity of burn were 2nd degree (superficial and deep) and in the remaining 5 patients (10%), it was 3rd or 4th degree. In 28 (56%), 1 (2%), 3 (6%), 35 (70%), 48 (96%), 19 (38%) and 6 (12%) patients IgG, IgM, IgA, IgG1, IgG2, IgG3 and IgG4 were lower than normal values, respectively. No significant correlation was seen between burn size (TBSA) and value of immunoglobulin (P>0.05). Although the drop in the serum concentration of immunoglobulins is irrespective to the burn size, more severe burn is associated with more decrease in the serum levels of IgA, IgM, IgG and its subclasses. However, further studies are needed to provide complementary data on this issue.

Cutaneous cytomegalovirus infection in a child with hyper IgE and specific defects in antibody response to protein vaccines.

Cytomegalovirus (CMV) infection is a common opportunistic systemic infection in immunocompromised patients, but skin involvement is rare. Herein, we report a 10 year-old girl from consanguineous parents who was referred to our center because of disseminated maculopapular rash. She had history of upper and lower respiratory tract infections. In immunological studies, increased serum IgE level and decreased responses to tetanus and diphtheria were detected. Polymerase chain reaction (PCR) examination of bronchoalveolar lavage and serum sample revealed the presence of CMV. Early diagnosis of cutaneous CMV and appropriate treatment are the key actions in management of patients with underlying immunodeficiencies to avoid further complications.

Cutaneous cytomegalovirus infection in a child with hyper IgE and specific defects in antibody response to protein vaccines

Cytomegalovirus (CMV) infection is a common opportunistic systemic infection in immunocompromised patients, but skin involvement is rare. Herein, we report a 10 year-old girl from consanguineous parents who was referred to our center because of disseminated maculopapular rash. She had history of upper and lower respiratory tract infections. In immunological studies, increased serum IgE level and decreased responses to tetanus and diphtheria were detected. Polymerase chain reaction (PCR) examination of bronchoalveolar lavage and serum sample revealed the presence of CMV. Early diagnosis of cutaneous CMV and appropriate treatment are the key actions in management of patients with underlying immunodeficiencies to avoid further complications.