Paediatric Sepsis_ Incidence, Ethiology, Evolution(1)

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    UNIVERSITY OF MEDICINE AND PHARMACY CRAIOVAFACULTY OF GENERAL MEDICINE

    PAEDIATRIC SEPSISdiagnosis, ethiology, evolution

    SUMMARY OF DOCTORAL THESIS

    SCIENTIFIC COORDONATOR: AUTHORProf. dr. Dumitru Bulucea Marinau Laura Daniela

    2010

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    CONTENTS OF DOCTORAL THESIS

    IntroductionAbbreviations

    Stage of knowledge-generalitiesChapter 1. INFECTION

    Chapter 2. BACTEREMIA

    Chapter 3. SIRS- Sistemic Inflammatory Response Syndrome

    Chapter 4. SEPSIS

    Chapter 5. SEVERE SEPSIS

    Chapter 6. SEPTIC SHOCK

    Chapter 7. MODS- Multiorgan Dysfunction Syndrome

    Chapter 8. HRA- Host response to aggression

    Chapter 9. TREATMENT OF PEDIATRIC SEPSIS

    Special section- Personal contributions

    Chapter 10. IMPORTANCE OF STUDIED PROBLEM. TARGETS.

    Chapter 11. MATHERIAL. METHOD OF WORK.

    Chapter 12. RESULTS

    Chapter 13. DISCUSSIONS

    Chapter 14. CLINICAL SEPSIS CASES PRESENTED.

    Chapter 15. CONCLUSIONS

    REFFERENCES (BIBLIOGRAPHY)

    KEY WORDS: infection, bacteremia, SIRS, sepsis, septic shock, MODS, treatment, incidence,ethiology, evolution, children, pediatric, mortality.

    SUMMARYThe doctoral thesis entitled Pediatric sepsis. Incidence, ethiology, evolution. extends for 212 pages andis structured according to criteria in force.At the beginning I had presented a list of abbreviations and a short introduction where I dot the actual

    problem of patients with sepsis.Starting with chapter 1 to chapter 9, I presented The Stage of Knowledge-generalities section, regardingthe definitions of infection, bacteremia, SIRS, sepsis, severe sepsis, septic shock, MODS, the actual dates

    of epidemiology, immunopathological mechanisms involved in manifestations and the diagnosis andtreatment in pediatric sepsis. The immunological mechanisms involved in appearance of SIRS

    manifestations have been largely presented, insisting on the role of humoral and cellular immune answerand on the importance of cytokines. Generalities finished with the treatment of pediatric sepsis.

    The Personal Contributions starts with chapter 10 to 15 and extends for 135 pages comprised six

    great themes: the aim of study, material and methods, results, discussions, presentation of 11 clinicalcases sepsis and conclusions.

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    Infection - definition: the invasion of microorganisms and their toxins into normally sterile places, ,,amicrobial phenomenon characterized by an inflammatory response (33).

    Localized infection is localized anatomic-pathologic inflammation and the common expression, but notmandatory - fever. Fever is defined as the temperature increased due to "reset" the thermoregulatory

    center in the hypothalamus by the action of cytokines (22): TNF, IL-1, IL-6, IFN. Small babies may behypothermic in response to disease or stress (15). FWS = FEO (fever without source or fever occultetiology) (22).

    Bacteremia is the presence of viable bacteria in the circulating blood (28, 34).Fungemie: presence of fungi in the circulatory stream (1, 28). Viremia: the presence of live viruses

    grown in blood (1).Occult bacteremia was defined as bacteremia without clinical signs of sepsis. Occult bacteremia only

    manifestation is fever or a cold sensation (42) and / or a minor infection (otitis media blue) andparaclinical, hemocultures positive (4). Transient bacteremia may occur after tooth extraction or otherminor surgical manipulations (endoscopy) (42).

    SIRS-systemic inflammatory response syndrome, involving at least two of the following events (1, 28,205):

    Tachypnea than 20 breaths / min; Tachycardia: consider (an adult) to over 90 beats / min;

    Fever or hypothermia: over 38 degrees (armpit) or below 36 degrees Celsius; Leukocytosis over 12000/mmc or leukopenia as 4000/mmc or presence of more than 10% of youngblood count forms. Infant SIRS = systemic response to infection manifested by two or more of the following: fever > 38.5 C (rectal) or < 36 C, heart rate> 2 SD above normal age, respiratory rate > 2 SD above normal age,WBC> 12 000 cells / mmc or below 4000 WBC / mmc or more than 10% young forms (33).Tachypnea of pediatric SIRS is defined thus: PCO2 below 32 mm Hg or mechanical ventilation / assisted

    for an acute process in the absence of secondary respiratory depression, neuromuscular diseases orgeneral anesthesia (84).Tachycardia in pediatric SIRS is characterized by: HR > 2SD above the normal value of that age, in theabsence of chronic HF or chronic medication and external stimulation (84). The following values areconsidered significant: infant HR > 180/min, 2-5 years, HR > 140/min, in children 6-12 years HR >

    130/min; HR > 110/min for 13 to 18 years of age ( 190).In pediatric site SIRS is permitted for children under one year bradycardia (instead of tachycardia)

    defined as: average heart rate below 10 percent for the corresponding age in the absence of external vagalstimulation, beta-blockers, congenital heart disease or unexplained low heart rate for a period exceeding

    30 minutes (150). In pediatric SIRS can not only diagnose on cardiac and respiratory frequency change(150).Infectious causes of SIRS: infections caused by bacteria, viruses, yeasts: pneumonia, erysipelas,infectious endocarditis, influenza, meningitis, pyelonephritis, appendicitis, cholecystitis, cellulitis,arthritis (33). Non-infectious causes of SIRS trauma, burns, acute pancreatitis, poisoning (33).

    In 1992, American College of Chest Physicians (ACCP) and Society of Critical Care Medicine (SCCM),in a consensus conference, set definitions for SIRS, sepsis, severe sepsis, septic shock, MODS. The terms

    were originally defined the adult sepsis, but were adapted from the 2000 (a) and in 2004, 2005, 2008 and

    for pediatrics (84, 182, 205).Sepsis = SIRS with a documented or suspected infectious etiology (94).Sepsis with negative cultures = SIRS + empirical antibiotic treatment for clinically suspected infection,but that all cultures are negative. Sepsis-pathophysiology concept, refers to those situations in which a

    clinically proven or suspected infection, localized or disseminated, is accompanied by a systemicinflammatory response in the body (SIRS) (42).The severe sepsis is defined as: sepsis associated with hypotension or signs of hypoperfusion - at least

    one acute organ dysfunction, such as metabolic acidosis, acute altered mental status, oliguria orARDS -Adult respiratory distress syndrome (94). In July 2006, recommendations for management of severe

    sepsis in pediatrics (31), in addition to SIRS and documented or suspected infection and other criterialisted in the definition, namely the presence of at least one of the following (criteria for severe sepsis

    taken and adapted from Bryant Nguyen (31) and Levy and collaborators (140)):

    -altered mental status (lethargy or coma gr. I), significant edema or positive fluid balance (over 20 ml / kgin 24 h);

    -hyperglycemia (120 mg / dl or 7.7 mmol / l) in the absence of diabetes;

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    -PCR> 2SD from normal age and / or Procalcitonin> 2SD from normal ( 70mmol / l);

    -Hyperlactatemia (lactic acid > 2mmol / l);-Ileus dynamic.

    -Cardiac Index> 3.5 L / m; arterial hypoxemia (PaO2/FiO2

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    mortality (256, 258). Most cases have been reported in infants and at the age of teenager (257, 258). Of 1586 253 hospitalizations in children under 19 years were 42 364 cases of severe sepsis which is a

    percentage of 2.6% and the percentage of hospitalizations for sepsis was 0.56 cases/1000 pediatricpopulation (258). The conclusion of the 2004 report of French doctors Dr. Pierre Tattevin and staff, was

    that severe sepsis was responsible for 7% of all deaths under 16 in 2003 in France (232).The incidence of neonatal sepsis is estimated at 1-2/1000 live births at term and 4-8/1000 at pretermneonates (186). Sepsis prevalence is much higher in immunosuppressed patients, admitted to Onco-

    Hematology, Surgery, ATI and Infectious Diseases. It is estimated that 30% of hospital surgical deathsbased septic cause (188).

    Numerous publications in the years 2001-2009 dealing with the adaptation and application of concepts ofbacteremia, sepsis, severe sepsis, septic shock, MODS for pediatrics (84, 170, 205). It had to debate this

    topic of great interest as a conference for nurses, "New Insights / New Outlooks on Sepsis" (VirginiaSims 2004) (205). An important consensus conference to define pediatric sepsis was in 2005:"International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction inPediatrics" (84).However, in Romanian language there is a relatively small number of publications that deal with the

    pediatric sepsis. In Romania, the exact incidence of pediatric sepsis is not known, as mortality of sepsis inthe infant population is not reported.

    The idea of this work started from the ignorance of the exact incidence of sepsis, its etiology andmortality of sepsis in Clinical Pediatrics and Pediatric Infectious Diseases in Dolj County. It is importantto recognize early infectious SIRS and MODS, septic shock also in the cases with negative culture and avigorous treatment of intensive care unit.The objectives targeted by this study: The calculation of sepsis incidence (including severe sepsis, septic shock and MODS) in the PediatricClinic and Pediatric Infectious Disease Clinic for the years 2006, 2007, 2008, 2009.

    The establishment of demographic characteristics of child population groups analyzed (according to theaverage distribution, age group, sex).The etiology of the sepsis cases studied. The elucidation of risk factors for sepsis and the establishment of the negative prognostic factors (riskfactors for death by sepsis).

    The evaluation of diagnostic criteria for sepsis, severe sepsis, septic shock and MODS for the casesstudied, the proposal of a diagnostic score for severe sepsis, septic shock and MODS.

    The evaluation of the cases studied the evolution and complications, mortality estimates. The evaluation of treatment in cases studied

    1.WORKING MATERIAL We conducted a comprehensive study, which refers to four groups of patients hospitalized in the PediatricClinics Emergency Hospital Craiova and Infectious Diseases, Department of Pediatrics, in PediatricSurgery Clinic, respectively, at various times included in the interval 2001-2009.There were studied: one main group composed of 575 patients aged between 0 and 16 years who were

    hospitalized, in a period included within 01-01-2006 to 31- 2-2009, a total of 578 hospitalizations withsepsis in Pediatric Clinic and Pediatric Infectious Diseases Clinic. This group was analyized as a

    prospective study.

    -L.nr.2 composed of 41 children between 0 and 16 years with a diagnosis of "septicemia" admittedbetween 01. 01. 2001-31. 12. 2005 in two clinics of Pediatrics at the Emergency Hospital Craiova. Thestudy of this group had a retrospective character.L.nr.3-consists of 23 cancer patients aged 0-16 years who were hospitalized in the period 01/01/2001 to

    30/06/2008 in Pediatric Clinic, Hematology-Oncopediatric compartment, having sepsis as secondarydisease; they totaled 25 hospitalizations, because two patients had two septic episodes.-L.nr.4 of 0-16 years included 47 patients with osteomyelitis, septic onset, abrupt or insidious, who were

    hospitalized and treated in the Pediatric Surgery Clinic in 2001-2007.The study of the last two groups had both a retrospective and a prospective character.

    Parameters evaluated in the patients of the study:- sex, age, place of origin of patients;

    -patient hospitalization period (month, year) and number of days of hospitalization;

    -criteria for diagnosis of sepsis, resulting from: hospital grounds, given the clinical examination onadmission and development, laboratory investigation: radiological images;

    -treatment;

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    -evolution of the patients;-anatomical -pathological examination for dead.

    2. METHOD OF WORK

    A statistical method was used: clinical data were entered into the computer and were made by calculating

    the arithmetic operations, percentages, ratios statistics.

    RESULTSResults for L1 group. The group of 575 children, having 578 admissions, 279 hospitalizations for sepsis

    have been at the Hospital for Infectious Diseases, and 299 hospitalizations with infectious SIRS were inPediatrics Clinic.

    The incidence of sepsis by year of study.Out of 20859 admissions (the total number in four years), we found 578 sepsis cases. The incidence of

    sepsis was 2,77%. The incidence for each year: 1,15% (60 cases) in 2006; 1,37%(70 cases) in 2007;2,4%(127 cases) for 2008; 6% (321 cases) for 2009.Out of the cases there were: 3% - newborns, infants 1-12 months- 34%, 30% -children aged 1-3 years,21% preschoolers, 12% pupils (8% between 7-12 years, 4% between 12 and 16 years).For the four years, the average percentage of positive cultures of all patients diagnosed with sepsis is only

    18%.Table no. 1.: The evolution of cases in 2006, 2007, 2008, 2009

    Year / Condition

    at discharge Healed Improved Transferred Dead Total2006 18(30%) 27(45%) 7(12%) 8 (13%) 60

    2007 25(36%) 28(40%) 9(13%) 8(11%) 70

    2008 60(47%) 47(37%) 11(9%) 9 (7%) 127

    2009 182(57%) 118(37%) 11(3%) 10(3%) 321

    Total 285(49%) 220(38%) 38(7%) 35(6%) 578

    Distribution of hospitalizations group 2006-2009 by SIRS criteria.

    Fever (hypothermia in newborns) and leukocytosis (or leucopenia or increased over 10% of youngelements in LF) were diagnostic criteria for 356 out of 578 patients; a major criterion along with theother two criteria (tachycardia, tachypnea) being used only for 56 children diagnosed with pediatric SIRS.Distribution of admissions by other laboratory investigations:Most of the children had a normal amount of platelets. 27% of patients had thrombocytosis (even

    thrombocythemia in ten of them) in the context of severe sepsis. Patients whose platelet count was notperformed were mainly those who died in the first two days of hospitalization, which were collected and

    worked fewer tests. Patients with thrombocytopenia had septic shock, MODS (with overt DIC).The number of cases increased ESR (301) is bigger than the number of children who had leukocytosis,

    and / or the elements of young blood count: 288. Most children had an increased sedimentation rate:52%.Out of 165 patients with increased ESR in 2009, 10 had very high: over 100 mm in one hour.Radiographs with interstitial matter have predominated in all years. Out of 578 admissions, 240 (42%)had radiological aspects of interstitial pneumonia. 87 patients (15%) had radiological confirmation ofbronchopneumonia, with the appearance of micro and macronodulars opacities. Other radiological aspects

    included: reticular appearance, reticulo-nodular, diffuse decrease in lung transparency, etc..Table No. 2. Distribution of hospitalizations group depending on the severity sepsis between 20062009

    Year Uncomplicated

    sepsis

    Severe Sepsis Septic shock MODS Total

    2006 25(41,5%) 25(41,5%) 3(5%) 7(12%) 60

    2007 36(52%) 22(31%) 5(7%) 7(10%) 70

    2008 74(58%) 40(32%) 5(4%) 8(6%) 127

    2009 249(78%) 52(16%) 13(4%) 7(2%) 321

    Total 384(66%) 139(24%) 26(5%) 29(5%) 578

    The complicated sepsis (severe sepsis, septic shock, MODS) was in 34% of cases.In L1, the percentage of children fully developed well psychosomatic is small (13%). Frequency of

    criteria defining sepsis complicated (severe sepsis, septic shock and MODS) in the years 2006 to 2009.The most common criterion was hypotension (clinical, TRC> 3 and "mottled") found in 67 children.

    Coma in varying degrees, hypoxia, lactatemia and hepatocytolisis were then, in sequence, the mostcommon criteria for sepsis complicated registered.

    The most common illness associated diagnosed for admissions throughout the four years (46% of the

    batch) is hypochromic (less iron)-infectious anemia. Protein-energy malnutrition (including weakness ofheight-weight) was recorded in 172 children (approximately 30% of the batch). Calculated frequency of

    obesity in the group: 1.57%. Common rickets (RCC) was recorded at 181 children, representing 31.31%

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    of the group. Hypocalcemia isolated in children older than 3 years, was noted in 50 patients, so for 8.65%of total, or 29% out of the group of children over 3 years. Very diverse malformations congenital or

    chronic diseases are in large numbers (119) found that secondary diagnoses in only 89 childrenhospitalized because 18 children were multimalformed.

    Infections that developed lethal anatomopathological confirmed: there were three cases ofmeningoencephalitis concomitant with bronchopneumonia and pericarditis and one case of endocarditiswere also associated with bronchopneumonia "in confluent foci. Six patients had two serious infections,

    fatal. Out of 35 who died, one alone had no chronic psychosomatic development.DISCUSSIONS

    The incidence of sepsis. Interpretation of survey results for group no. 1.Admissions for sepsis were 299 in the Pediatric Clinic and 279 in the Pediatric Infectious Disease Clinic.

    The average incidence of sepsis calculated for Pediatric Infectious Disease Clinic, having regard to all10016 hospitalizations for 2006-2009 was 2.78% The average incidence of sepsis, for the same years in Pediatric Clinic: 2.76%.C) Dynamics of the incidence of sepsis per year in the two clinicsThe incidence of sepsis has doubled in 2008 compared to 2006 (2.4% vs. 1.15%) throughout the two

    clinics, in a very close number of hospitalizations (5307 vs. 5299). Pediatric sepsis incidence in 2009 isnearly triple its value in 2008 and four times higher than its 2007 value, five times higher than the

    incidence in 2006. The value of 6% is close to the minimum estimated incidence of sepsis in Intensivecare units of Infectious Diseases -6.3% in the U.S.A. (208).The incidence of sepsis in the U.S. increased by 8.7% per year between 1979 and 2000 from 82.7 to 240.4per 100,000 inhabitants (149). The average incidence we found: 2.77% is close to that of Americanliterature, found by R. Scott Watson and colleagues in 2003: 2.67%-for the severe pediatric sepsis (258).Peaks of incidence of cases of sepsis the years 2006-2009 for the months of summer were noted in Julyand August(73 admissions). The incidence is high in November, too (55 children).

    There have been many cases in the summer months, the peak incidence was in August. For bacteremia,the peak is early spring to late autumn in children of all ages and is due to viral respiratory infections andgastro-intestinal. Another peak occurs in summer and bacteremia is due to enterovirus infections, anddeficits in thermoregulation in hot weather (59).Demographic characteristics of child population groups

    a) The structure of groups of hospital patients after sexStructure hospitalizations batch 2006 - 2009 by gender: 333 boys and 245 girls; 58% boys and 42% girls.

    The ratio between the total number of boys and the total number of girls is 1.35, in agreement with theresults of French doctors who have found a predominance of male patients with septicemia B / F = 1.3

    (232).b) The distribution of patients by area of originFor L1: 55% in urban areas and 45% in rural environment. For 2008, cases of sepsis had distribution byarea of origin identically to the current population distribution in Dolj County: 54% in urban areas and46% in rural areas (population distribution was that in Dolj at 01/01/2010).

    c). Number of cases of sepsis is inversely proportional to age. The category under three years were 67%out of total registered cases, infants being 37%.

    The risk of contracting bacterial infection is higher in young children 0-3 years (268): they are deficient

    in immunoglobulin G, antibodies to encapsulated bacteria, macrophage function is insufficient andreduced neutrophil activity (15). Small age, less than three years, with a weight of 0.67 in the squad, is amajor risk factor for sepsis; we give a score 1.The etiology of sepsis. Underlying factors

    -For studied years, the average percentage of cases with positive cultures of all patients diagnosed withsepsis is only 18%. 112 bacteria were detected in 105 cases (7 septicemia being double etiology): 62 grampositive, 48 gram negative, two Candida albicans. Among those with septic shock, only one was clarified

    the etiology, who also survived.- 55% of the detected germs are Gram positive: Staphylococcus Aureus, Staphylococcus White hemolytic,

    streptococcus, pneumococcus. Prevail staphylococci (56 of 62), the most important being StaphylococcusAureus. Among gram-negative, the most significant percentage wereE. coli and Klebsiella: 64.6% (31 of

    48).

    -There have been seven cases of sepsis with dual etiology in 4 of these, staphylococci were associatedwith gram-negative and in 2 blood cultures with C. albicans; only one association noted between gram

    negatives (E. coli to Klebsiella).

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    - There were three cases of chickenpox infected, in 2009 and one in 2008; all four patients were infectedwith Staphylococcus aureus (detected in blood culture). We could say that both chicken pox, rotavirus

    enterocolitis, (two in 2009) and ,respectively, AH1N1influenza (one case in December 2009) favored bytransient immunosuppression Staphylococcus aureus sepsis.

    Lower respiratory tract infections (interstitial pneumonia, bronchopneumonia) are the main initiator ofsepsis cases in this study (43%). Erythemato-purulent acute tonsillitis accounts for 14% and then, mostimportant, gastroenterocolitis(11%). Follow urinary tract infections and then meningoencephalitis, in the

    etiology of pediatric SIRS cases analyzed. Mucocutaneous infections, septic arthritis and celulitele were afew cases. In the literature, are cited in the etiology of SIRS: pneumonia, endocarditis, and

    meningoencephalitis (33).Chronic software development promotes sepsis by suppression of immunity.

    Evaluation of diagnostic criteria for severe sepsis, septic shock and MODS wasmade and also a proposal of a diagnostic score for complicated sepsis.Useful examples used in the study: Sepsis+ coma gr.1 or sepsis + hepatocytolisis or sepsis+ dynamic ileusor sepsis + PF were diagnosed as "severe sepsis" (score 4). To diagnose a septic shock, we needed ascore of at least 6. Examples:

    Severe sepsis + hypotension >1 hour or Sepsis +coma-I degree + hypotension >1 hour.For diagnosis of MODS was needed a score of at least 7. Examples:

    - Sepsis + average coma + RA (creatinine > 3.5 mg / dl, urea > 100mg/dl) or-Sepsis + average coma.+ mechanical respiratory.

    CONCLUSIONS

    It was noted a slight increase in the incidence of pediatric sepsis in 2007 compared to 2006 (1.37% vs.1.15%). As particulary, cases of sepsis were complicated, the incidence increase from the 1.15 to 1.37%(dr.Tattevin and collaborators reported for septicemia, estimated at 1-2%). The incidence of sepsis in 2008 (2.4%) is closest to the average value of four years and almost similar to

    that reported in 2001 by Angus and colleagues in the U.S.: 2.26% for infectious SIRS. The average incidence of sepsis for the years 2006-2009 we found it for L1-2.77% which is closed tothat reported by Scott Watson and collaborators: 2.6%, for the severe pediatric sepsis. The incidence of sepsis was diagnosed in Pediatrics clinics in Dolj County study, in agreement withliterature data, is increasing due continue postgraduate education of doctors, improved methods of

    diagnosis and ,possibly, due the selection of microbial strains extremely virulent, nosocomial orcommunity through excessive antibiotics.

    There have been many cases in the summer months, the peak incidence was in August (73 admissionswith sepsis) because of enteroviral infections and deficits in thermoregulation in hot weather.

    The boys dominated all patients with sepsis (58%), like in reports of American and French researchers.The ratio between the total number of boys and the total number of girls is 1.35, according to Frenchmedical outcomes in patients with sepsis who have found a predominance of male B / F = 1.3. The 0-3 years age group there were 67% of all cases (of which 37% were infants). In cases L2 groupunder 3 years of age is 83%.

    Most admissions of L1 from urban areas (53%) because more than half the children residents of DoljCounty live in cities (54.02% of the population is urban, the remainder in rural areas). Between cases

    batch # 2, Lot No. 3, Lot No. 4 (most severe) patients predominate in rural areas because of low levels of

    healthcare and health education in rural areas. For L1, the average percentage of cases with specified etiology is 18%. Out of 35 deaths, the etiologywas established at a rate of 17%. Out of 26 with septic shock, for only one was able to determine theetiology, who also survived. In group L3, the etiology was clarified at 65% of patients.

    The etiology of sepsis in the years 2006-2009 (L1) is dominated by gram-positive: 55% of germsdetected, the most important being Staphylococcus. Also, for L2, L3, L4 the most commonly germ wasStaphylococcus aureus, detected in percentage of 66-73%.

    Antibiotic to which staphylococci were most sensitive (> 50%) was Linezolid, followed by Oxacillin. Ingroup L3, primarily, staphylococci were sensitive to cephalosporins.

    Respiratory infections (interstitial pneumonia, bronchopneumonia) are the main initiator of sepsis(43%), followed by mixed respiratory infections, then digestive (18%). These results are consistent with

    the findings of U.S. researchers, who reported first in the etiology of sepsis pneumonia in children greater

    than a month. The main predisposing factors for sepsis, we found immunodepression by malignancy, age under 3

    years and anemia, and that secondary factors: dystrophy, rickets, congenital diseases, male sex.

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    Found Negative prognostic factors were: granulocytopenia, age less than 1 year, anemia, birth defects,male sex, in patients diagnosed with bronchopneumonia and / or meningoencephalitis.

    15% of children with sepsis were associated with congenital diseases. Out of these, 11 children hadsingle or multiple heart malformations which represents a 1.9% incidence of MCC in L1.Out of the 35

    children who died, 18 (51%) had congenital malformations. Major Diagnostic criteria for sepsis werefeverand leukocytosis > 12000, in the presence of infection in61% of children studied. 10% were enrolled on two major criteria related to fever and increased PMNns

    over 10% and 29% based on the combination of a major criterion with two minor (tachypnea andtachycardia clinically evaluated only).

    Complications of the most important statistic, which constituted the criteria for complica ted sepsis:hypotension (diagnosed in 67 cases), coma, noted in 63 children, severe hypoxia was found in 45 patients

    and hepatocytolisis, highlighted paraclinical in 43 children. Cases of sepsis were most uncomplicated, in groups 1 and 4. Sepsis complica ted software dominated theL2 and L3 groups: in group 59% L2, and L3 with a drop of 92%. Sepsis complicated site, 34% of L1, included: the severe sepsis in 24%, septic shock (5%) and MODS(5%). In the group L2, septic shock was 24% of cases, and L4, only 7% of admissions with osteomyelitis,

    sepsis onset.Mortality of 6% of L1, is close to that cited by Burdette. We found a mortality of 69% for cases of

    MODS. In medical literature, MODS mortality is estimated at 75-100%. Mortality due to septic shock inour study we found 58%, which is higher than expected overall mortality due to septic shock (40-50%).Complicated sepsis mortality was 18% (35 deaths of 194 sepsis complicated) in L1. Bronchopneumonia was the most frequent anathomopathological diagnosis (26 of 35 deaths). Purulentmeningoencephalitis anathomopathological diagnosis was second (10 of 35). The group L2, have been fatalities as a percentage of 19.5%. Mortality was highest in group L3: 32%.Mortality was 7% in the L4 group.

    The most effective antibiotics were III and IV generation Cephalosporins combined withaminoglycosides and the Carbapenems. Severe infections remain a significant pathology even in the era of antibiotics.

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    CURICCULUM VITAE

    Name : MARINAU LAURA DANIELA Date of birth: 29. 09. 1967. Marital status: married, 3 sons;Address: CRAIOVA, Riului street, no177.

    2. Educational backgroundFrom sept.2000-Primary Medicine Pediatric Doctor; from oct.1996 University Assistant in UMF

    Craiova.

    Dec.1996- Specialist Physician Pediatric (Internal Medicine for children); 1992- Residency, Bucharest,promoted on 38-th position; 1985-1991- University of Medicine and Pharmacy Carol Davila-

    Bucharest - Faculty of General Medicine graduated in sept. 1991;1979-1985- Nicolae Balcescu (Carol I) High school Craiova; 1973-1979- Primary and first part ofSecondary School, no-9 Craiova.3. Competences, member in societies, courses, congresses, papersCourses:

    - 2 long term courses: in one year Psicho-Pedagogy(graduated in sept 2009); Medical Informatics(4months, finished in 2008); 5 short courses of 1-3 months.

    Congresses:

    - Congresses and Conference organized by National Societies: 12 participations

    - Other Medical Symposiums-30 participationsExtensive papers:- First author : 3

    - Joint author: 2Summary papers, posters:

    - first author: 26- joint author: 12Professional Experience:

    1 job in Clinics of Childcare in Craiova (oct. 1996-dec.1998)2 Specialist Pediatric Physician in City Hospital Bals (01.02.1996-30.09.1996)3 Resident Medicine Doctor (01.02.1994-31.01.1996) in Emergency County Clinical Hospital Craiova: 2

    years; Pediatric Hospital Timisoara: 1 year (02.12.1992- 31.12.1993)

    Present jobFrom jan. 1999 job in Pediatric Clinic of Emergency County Clinical Hospital Craiova,from 1996 University Assistant in UMF Craiova.