Tehran University Medical Journal

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Sepsis is the systemic response to severe infection in critically ill patients. Sepsis, septic syndrome & septic shock represent the increasingly severe stages of the same disease. Despite the remarkable improvements in outcome, sepsis & septic shock remain an important cause of morbidity & mortality in children. This is a retrospective study among the patients who were admitted in the pediatric intensive care unit (PICU) of Children's Hospital Medical Center from Farvardin 1371 till Esfand 1375. During this period 4018 children were admitted in the PICU, 138 of these patients (3.4%) had the initial diagnosis of sepsis or septic shock. The age of these patients were from 3 months to 14 years (mean of 23.5 months). The male to female ratio was 2.1:1. Out of these 138 patients only 16 cases (11.6%) had sepsis and the others (88.4%) had criterias of severe sepsis or septic shock. Multiple Organ Dysfunction (MOD) were found in 96 cases (69.3%). Diarrhea was the most common primary disease that resulted in sepsis or septic shock. Only 20.3% of the cultures were positive, among which E-Coli was the most in 8.7%, Staphylococcus aureus in 5.7%, Klebsiella in 2.9% and pseudomonas in 1.4%. 66.7% of these patients expired, the mortality rates of the patients with severe sepsis or septic shock that concommitantely had MOD were higher than the other (P<0.0005). So it may be better if children with clinical diagnosis of sepsis be hospitalized in an intensive care unit or at minimum in a facility that can closely monitor these patients during the initial stabilization period.

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Background: Sepsis is the leading cause of death in critically ill patients throughout the world. The incidence is increasing despite the major advances in the development of antimicrobial agents and other supportive treatments. Based on multiple studies, it has been shown that patient outcome depends on Th1 and Th2 cytokine response. Moreover, whenever the Th2 response is predominant, the sepsis is more severe. The aim of this study was to evaluate the correlation between cytokine levels and the severity of sepsis in patients.
Methods: A cross-sectional study on the cellular levels of several pro-inflammatory cytokines was carried out in patients with sepsis and severe sepsis. The study included 37 patients (24 men and 13 women), 26 of them had sepsis and 11 had the severe form of sepsis Thirty-seven healthy volunteers served as controls. The average age of the patients was 57 years (±23.3 years), with a range of 21 to 92 years. From the whole blood of the subjects, we separated the monocytes and leukocytes, which were then cultured. Using an ELISA method, we measured levels of IFN- and IL-12 (associated with Th1), and IL-4 and IL-10 (associated with Th2) in the cultured cells with and without cell stimulation.
Results: No correlation was found for IFN- production in the cells of patients with sepsis and severe sepsis, regardless of whether the patients had died or survived. However, IL-12 levels were significantly decreased in severe sepsis compared with those of sepsis patients (P=0.048). Furthermore, the cells of expired patients also had significantly decreased IL-12 levels compared with those of surviving patients (P=0.028). We also found that the levels of IFN-, IL-4, and IL-10 were decreased in patients compared with those of controls, which correlated to their production. However, there was no correlation for IL-12 production between the cells of the patients compared with those of the controls. There was also no correlation for cytokine production between men and women with sepsis and in adults compared with that of elderly patients (>55 years old).
Conclusion: We have shown that the predominating T helper cell subset in patients with severe sepsis, as well as expired patients, is Th2. In conclusion, the correlation of Th1 cytokine production and progression of sepsis was demonstrated. Most probably IL-12 levels would be significantly lower in patients with severe sepsis and those who expired.

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Background: To identify the clinical manifestations and mortality rate among neonates with early- and late-onset sepsis.
Methods: We retrospectively reviewed the hospital records in Children’s Hospital Medical Center, Tehran University of Medical Sciences of 104 neonates (50 females and 54 males) diagnosed with septicemia and treated from September 1994 to August 1995. Diagnosis of septicemia was based on standard criteria. According to the time of onset of disease, there were 50 neonate with early-onset and 54 with late-onset septicemia.
Results: Of the clinical signs in the 104 patients, respiratory signs were found in 31 patients, poor feeding in 57, jaundice in 42, apnea in 25 and hyporeflexia in 25. Blood cultures were positive in 31 (34.8%) of the neonates: the most common species isolated was Staphylococcus aureus with eight cases, while five had Staphylococcus epidermidis, all of whom had a single species of bacterium isolated. Seventy-three (70%) had normal birth weights (equal to or heavier than 2500 g) and 31 (30%) were classified as low birth weight (birth weight less than 2500 g). Cerebrospinal fluid culture was positive in four (6%) of the patients, including one case of Escherichia coli, one Salmonella typhi, one Klebsiella, and one Staphylococcus aureus. The frequency of infection in male and female infants was 53% and 47%, respectively. Among the infants with early-onset sepsis, 16 (32%) were low birth weight. Overall, the mortality rate among these patients was 30%, including 18 out of the 50 with early onset and 14 out of the 54 with late onset sepsis. Of these infants, 23 had meningitis, including 13 (26%) with early-onset sepsis and 10 (9.6%) with late-onset sepsis. Among the low birth weight infants, the mortality rate was higher (42%) than that of the infants with normal birth weight (26%).
Conclusion: Because of the high mortality rate among low birth weight neonates with sepsis, we suggest that this group of patients should receive more care and there should be greater effort to ensure that they are treated with the appropriate antibiotics. Furthermore, all healthcare givers responsible for the management of neonates with sepsis should receive additional continuing education courses to ensure that they are aware of the risks, complications and mortality rate among these patients.

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Background: Rationalize of drug use in societies is one of the main responsibilities of health policy makers. In our country irrational use of dugs has increased in the recent years, for example one study in 1998 has shown that average number of medicines per prescription was 3.6, percentage of prescriptions containing antibiotics was 43% and percentage of prescriptions containing Injections was 39%. One of the best tools for evaluation of drug use is the WHO guideline for calculating prescribing indicators. In this study, we had an assessment about prescribing patterns in South of Tehran, Islamshahr and Rey Health Centers.
Methods: In order to evaluating prescribing indicators in Tehran University of Medical Sciences region 35 facilities which had pharmacy were selected according to WHO gridline and 4190 prescription from these facilities were studied. Indicators were calculated according to formulas has explained in article. Results: The average number of drug per prescription was 2.58, percentage of drug prescribed by generic name: 99.8%, percentage of encounters prescribed Antibiotics: 62.39% percentage of encounters prescribed Injection: 28.96% & the percentage of drugs prescribed from PHC formulary 99.46%. These findings were almost similar in the three Health Centers.
Conclusions: Health facilities are one of the most important bases to improve rational use of Drugs and general practitioners are the major chain in RUD cycle. Results show that we need to design intervention especially educational interventions to improve two WHO prescribing indicators, percentage of encounters prescribed Antibiotics & Injections in this region. For reaching this goals we need to design educational programs for physicians, pharmacists and people too. These educations can be as workshops, seminars, conferences or printed materials such as books, leaflets and etc

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Background: Sepsis is the leading cause of hospital admission and mortality. One marker for differentiation between infectious and non-infectious diseases is serum procalcitonin (PCT) level. The goal of this study was evaluation of serum procalcitonin level for differentiation among infectious & non infectious systemic inflammatory response syndrome (SIRS).
Methods: In a cross sectional study 263 patients with probable symptoms of sepsis that admitted to emergency department of Imam Khomeini Hospital Complex in Tehran, Iran, between 2006 and 2008, were evaluated for serum procalcitonin level by semi quantitative method. The clinical findings, demographic and laboratory data were identified by reviewing the medical notes.
Results: A total of 263 patients enrolled in the study. Mean age in study patients was 46.9 year (20.7) and most of the patients were male (65.8%). In 104 patients (39.5%) serum procalcitonin level was less than 0.5 (ng/ml), in 49 patients (18.6%) was between 0.5 and 2 (ng/ml), in 74 patients (28.1%) was between 2 and 10 (ng/ml) and in 36 patients (13.8%) was more than 10 (ng/ml). Sixty three patients (60.6%) with PCT<0.5ng/ml, had non-infectious SIRS, while all patients with PCT≥10ng/ml, had infectious SIRS. Procalcitonin level in patients with infectious SIRS was significantly more than patients with non-infectious SIRS (p<0.0001). Sensitivity of test for cut off point of 0.5, 2 and 10 (ng/ml) were 89.2%, 67.1% and 22.8% respectively, and its specificity for cut off points of 0.5, two and 10 were 82.9%, 96.2% and 100% respectively.
Conclusions: Procalcitonin level in combination with an appropriate clinical assessment can help us in beginning of antibiotic therapy timely and improve diagnostic and prognostic evaluation of patients with sepsis.

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Background: Sepsis is one of the most important causes of mortality in severely ill ICU patients. At least, a part of high mortality rate in sepsis patients is due to less specific clinical symptoms for prompt diagnosis. Recently some studies report that serum levels of procalcitonin will increase in these patients but changes of serum levels following treatments is not known. This study was designed to determin procalcitonin levels in patients with bacterial infectious disease in ICU, initially and during therapy and compare the levels during response to treatment.

Methods: This prospective cross-sectional study was conducted on ICU patients with infectious diseases, blood specimen collected on day 1 and then in days 3 and 7 of ICU admission. The semi-quantitative PCT-Q test was performed.

Results: Thirty five patients, 22(62.9 %) men and 13(37.1%) women, were enrolled in this study. 18(51.4%) patients died. Procalcitonin level in most patients in admission day was more than 10 ng/ml [16 (45.7%)] but in patients that react to treatment, decline to lower than 0.5 ng/ml [14(77.8%)]. Mean rank of procalcitonin level from 1.14 ng/ml in first day reached to 2.72 ng/ml in seventh day (p<0.0001).

Conclusions: This study showed that serum procalcitonin levels in ICU patients with bacterial sepsis significantly decrease following response to treatment. The measurement of serum procalcitonin in ICU patients with bacterial infectious diseases at first arrival day and following treatment is recommended.

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Background: Bacterial sepsis is a main cause of mortality and morbidity especially in preterm newborns. The aim of this study was to search the bacterial etiologies of neonatal sepsis in NICU admitted preterm neonates.

Methods: A descriptive cross-sectional study had done in NICU of Ali Asghar Hospital, Tehran, Iran from March 2007 to March 2009. Seventy septicemic preterm newborns (<37 weeks) were studied. At admission day, for blood culture, 1-2 ml of venous blood was drawn after swabbing the venipuncture site with alcohol. After centrifugation of blood samples, deposits were cultured on sheep blood agar and incubated in a candle jar at 37 °C for 48 h and followed by subcultured. Isolates were identified using standard techniques (Nima pouyesh, Iran). Type of isolated bacterial organisms determined. Its correlation with gestational age, birth weight, premature rupture of membranes (PROM) and other variables determined we used the nonparametric two independent sample test, Mann-Whitney U test. Chi-square values (CI 95%, P< 0.05) were calculated for all categorical variables. P-value less than 0.05 considered statistically significant.

Results: Of 70 studied septicemic preterm cases, 17 (10.6%) cases had positive blood culture. Overall gram-negative organisms were more frequent than gram-positive organisms, Klebsiella (K.) pneumoniae, Escherichia (E.) coli and Staphylococcus (S.) aureus organisms were the 3 common causes of bacterial sepsis in studied cases. Early onset sepsis produced by K. pneumonia (40%), E. coli (20%) and S. aureus (20%). K. pneumonia, E. coli, S. aureus had equal incidence in late onset sepsis (26.8%). K. pneumonia was more frequent in early onset sepsis (P= 0.05), and in low birth weight (< 1500 g) neonates (P= 0.005, and PROM (P= 0.05).

Conclusion: Three causes for sepsis in premature newborns were determined: K. pneumonia, E. coli and S. aureus, it is so important for initial antibiotic treatment in admission day. Low birth weight, prematurity, and, PROM were the common risk factors for sepsis in cases. By preventing of low birth weight, low gestational age, and PROM the risk of sepsis could be decreased. We recommend empiric antibiotic in septic preterm newborns which can cover: K. pneumonia, E. coli and S. aureus in our center.

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Background: In the present study, we hypothesized that conditioned medium (CM) derived from mesenchymal stem cells attenuates the brain oxidative stress in sepsis induced by the cecal ligation and puncture (CLP) model.
Methods: This study was performed in the Department of Physiology at Tehran University of Medical Sciences from August 2018 to April 2019. Conditioned medium was collected from mesenchymal stem cells isolated from rat's adipose tissues at the second culture passage. Male Wistar rats weighting (220-250 g) were randomly divided into three experimental groups (n=8 each): Sham, Sepsis and CM. Sepsis was induced by cecal ligation and puncture model in the Sepsis and CM groups. Animals in the CM group received the conditioned medium from 5×10⁵ mesenchymal stem cells (2 h after sepsis induction, i. p., 3-5 mL). The systolic blood pressure and O2 saturation were measured 24 h after the treatment. The plasma and brain tissue samples were taken for inflammatory and oxidative stress assessment, respectively.

Results: Septic rats showed a significantly lower systolic blood pressure and O2 saturation level. They also had a significant increase in the plasma inflammatory indices (tumor necrosis factor-alpha [TNF-α], interleukin-6 [IL-6]) and brain malondialdehyde (MDA) content as well as a significant reduction in the brain superoxide dismutase (SOD) activity compared to the Sham group. The CM group had significantly higher systolic blood pressure and O2 saturation level compared to the septic rats. The animals in the CM group showed a significant attenuation in the plasma inflammatory indices (TNF-α and IL-6) and brain MDA content while having a significantly higher brain SOD activity compared to the Sepsis group. Conclusion: Our findings showed that conditioned medium derived from mesenchymal stem cells has protective effects in preventing the inflammatory and oxidative stress status and may be suggested as a promising treatment in patients suffering from sepsis and septic shock.

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