Bakterielle Infektionen bei Neugeborenen. Leitlinie der GNPI, DGPI, DGKJ und DGGG. (S2k-Level, AWMF-Leitlinien-Register-Nr. 024/008, April 2018)

Leitlinienreport

1 Fassung 06/1997

2 Fassung 02/2006

3 Fassung 04/2018

Redaktionskommittee der 3. Fassung

Von der Gesellschaft für Neonatologie und Pädiatrische Intensivmedizin (GNPI) wurden mandatiert:

• Michael Zemlin, Homburg/Saar (federführend)

• Angelika Berger, Wien

• Christoph Härtel, Lübeck

• Helmut Küster, Göttingen

• Andreas Müller, Bonn

• Frank Pohlandt, Ulm

Von der Deutschen Gesellschaft für Pädiatrische Infektiologie (DGPI) wurden mandatiert:

• Axel Franz, Tübingen

• Christian Gille, Tübingen

Von der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG) wurde mandatiert:

• Waltraud Mer, Bonn

Beratende Mitwirkung:

• Arne Simon, Homburg/Saar (AG Antibiotic Stewardship der DGPI)

 

MissingLinkText

Suchstrategie

Bei der Überarbeitung der Leitlinie wurden zwischen 2015 und 2017 die Datenbanken MEDLINE (https://www.ncbi.nlm.nih.gov/pubmed/) und The Cochrane Library (http://www.cochranelibrary.com/), die Webseite National Institute for Health and Care Excellence (https://www.nice.org.uk), der American Academy of Pediatrics (https://aap.org), deutsch- und englischsprachige Lehrbücher, persönliche Unterlagen der Autoren sowie die in den identifizierten Publikationen angegebenen Referenzen durchsucht.

 

MissingLinkText

Verfahren zur Konsensfindung

Der Entwurf der aktualisierten Leitlinie wurde von den genannten Mandatsträgern im eMail-Umlaufverfahren erarbeitet und vorab formal in einer ersten internen Delphi-Runde einstimmig konsentiert. Per E-mail wurde der Entwurf am 2.3.2017 einer Gruppe von 39 Neonatologinnen und Neonatologen vorgelegt, die vom Vorstand der GNPI zu einer erweiterten Delphi-Konferenz zur Kommentierung eingeladen worden waren. Die Mitglieder wurden gebeten, den Entwurf kritisch zu lesen und Änderungsvorschläge an den Leitlinien-Beauftragten zu schicken. Die Verfasser der Kommentare blieben füreinander und für die Leitliniengruppe der Mandatsträger anonym. Die Änderungsvorschläge wurden vom Leitlinien-Beauftragten anonym den Mandatsträgern übermittelt. Diese nahmen Stellung zu den Änderungsvorschlägen, die teilweise übernommen wurden, und legten in der Folge einen 2. Entwurf vor. Das überarbeitete Dokument wurde am 7.11.2017 erneut der erweiterten Delphi-Konferenz zur Kommentierung zugeleitet. Die Kommentare der 2. Erweiterten Delphi-Runde wurden offen an alle Mitglieder der erweiterten Delphi-Runde und der Leitliniengruppe übermittelt. Insgesamt beinhalteten 32 von 33 abgegebenen Voten eine Zustimmung zum revidierten Text des Entwurfs. Unter Berücksichtigung redaktioneller Änderungswünsche aus der erweiterten Delphi-Konferenz wurde eine Endfassung erstellt, die von den Mandatsträgern in einer erneuten internen Runde einstimmig angenommen wurde. Die Endfassung wurde am 30.04.2018 den Vorständen der beteiligten Fachgesellschaften zugeleitet. Die Leitlinie wurde von den Vorständen der vier tragenden Fachgesellschaften am 4.6.2018 (DGGG), 6.6.2018 (GNPI), 26.6.2018 (DGPI) und 20.8.2018 (DGKJ) verabschiedet.

Erstellungsdatum

04/2018

 

MissingLinkText

Letzte Überarbeitung

01/2019

 

MissingLinkText

Nächste Überprüfung geplant

01/2023

 

MissingLinkText

 

MissingLinkText

• Literatur

• 1 Wynn JL, Wong HR, Shanley TP. et al. Time for a neonatal-specific consensus definition for sepsis. Pediatric critical care medicine: A journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies 2014; 15: 523-528
• 2 AWMF. Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften. S2k-Leitlinie 024-020 “Prophylaxe der Neugeborenensepsis – frühe Form – durch Streptokokken der Gruppe B”. 2016 [updated 2016/03/09. Available from http://www.awmf.org/leitlinien/detail/ll/024-020.html http://www.awmf.org/leitlinien/detail/ll/024-020.html
• 3 Schwab F, Zibell R, Piening B. et al. Mortality due to bloodstream infections and necrotizing enterocolitis in very low birth weight infants. The Pediatric infectious disease journal 2015; 34: 235-240.
• 4 RKI. Robert Koch-Institut. Definitionen nosokomialer Infektionen (CDC-Definitionen). 7 ed: NRZ Nationales Referenzzentrum für Surveillance von nosokomialen Infektionen 2011
• 5 Garner JS, Jarvis WR, Emori TG. et al. CDC definitions for nosocomial infections. American journal of infection control 1988; 16: 128-140.
• 6 NRZ. Nationales Referenzzentrum für Surveillance von nosokomialen Infektionen. KISS (Krankenhaus-Infektions-Surveillance-System). updated 2015/04/16. Available from http://www.nrzhygiene.de/surveillance/kiss/
• 7 Ussat M, Vogtmann C, Gebauer C. et al. The role of elevated central-peripheral temperature difference in early detection of late-onset sepsis in preterm infants. Early human development 2015; 91: 677-681
• 8 American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992; 20: 864-874
• 9 Weston EJ, Pondo T, Lewis MM. et al. The burden of invasive earlyonset neonatal sepsis in the United States, 2005–2008. The Pediatric infectious disease journal 2011; 30: 937-941
• 10 Wynn JL, Hansen NI, Das A. et al. Early sepsis does not increase the risk of late sepsis in very low birth weight neonates. J Pediatr 2013; 162: 942-8.e1-3
• 11 NRZ. Nationales Referenzzentrum für Surveillance von nosokomialen Infektionen. NEO-KISS (Surveillance System nosokomialer Infektionen für Frühgeborene auf Intensivstationen).updated 2015/04/16. Available from http://www.nrz-hygiene.de/surveillance/kiss/neo-kiss/
• 12 Puopolo KM, Draper D, Wi S. et al. Estimating the probability of neonatal early-onset infection on the basis of maternal risk factors. Pediatrics. 2011; 128: e1155-e1163
• 13 Didier C, Streicher MP, Chognot D. et al. Late-onset neonatal infections: Incidences and pathogens in the era of antenatal antibiotics. European journal of pediatrics 2012; 171: 681-687
• 14 Hornik CP, Fort P, Clark RH. et al. Early and late onset sepsis in verylow-birth-weight infants from a large group of neonatal intensive care units. Early human development 2012; 88 (Suppl. 02) S69-S74
• 15 Zaidi AK, Knaut AL, Mirrett S. et al. Value of routine anaerobic blood cultures for pediatric patients. J Pediatr 1995; 127: 263-268
• 16 Stoll BJ, Hansen NI, Sanchez PJ. et al. Early onset neonatal sepsis: The burden of group B Streptococcal and E. coli disease continues. Pediatrics 2011; 127: 817-826
• 17 Moore MR, Schrag SJ, Schuchat A. Effects of intrapartum antimicrobial prophylaxis for prevention of group-B-streptococcal disease on the incidence and ecology of early-onset neonatal sepsis. The Lancet Infectious diseases 2003; 3: 201-213
• 18 Geffers C, Haller S, Heller G. et al. Nosokomiale Infektionen bei Neugeborenen. Monatsschr Kinderheilkd 2014; 162: 385-393
• 19 Hartel C, Faust K, Avenarius S. et al. Epidemic microclusters of bloodculture proven sepsis in very-low-birth weight infants: Experience of the German Neonatal Network. PloS one 2012; 7: e38304
• 20 Tsai MH, Chu SM, Hsu JF. et al. Risk factors and outcomes for multidrugresistant Gram-negative bacteremia in the NICU. Pediatrics 2014; 133: e322-e329
• 21 Dong Y, Speer CP. Late-onset neonatal sepsis: Recent developments. Arch Dis Child Fetal Neonatal Ed 2015; 100: F257-F263
• 22 van de Laar R, van der Ham DP, Oei SG. et al. Accuracy of C-reactive protein determination in predicting chorioamnionitis and neonatal infection in pregnant women with premature rupture of membranes: A systematic review. European journal of obstetrics, gynecology, and reproductive biology 2009; 147: 124-129
• 23 Su H, Chang SS, Han CM. et al. Inflammatory markers in cord blood or maternal serum for early detection of neonatal sepsis-a systemic review and meta-analysis. Journal of perinatology: Official journal of the California Perinatal Association 2014; 34: 268-74
• 24 Kerste M, Corver J, Sonnevelt MC. et al. Application of sepsis calculator in newborns with suspected infection. The journal of maternal-fetal & neonatal medicine: The official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet 2016; 29: 3860-3865
• 25 Siriwachirachai T, Sangkomkamhang US, Lumbiganon P. et al. Antibiotics for meconium-stained amniotic fluid in labour for preventing maternal and neonatal infections. Cochrane Database Syst Rev 2014; Cd007772
• 26 Hutton EK, Thorpe J. Consequences of meconium stained amniotic fluid: What does the evidence tell us?. Early human development 2014; 90: 333-339
• 27 Modi N, Dore CJ, Saraswatula A. et al. A case definition for national and international neonatal bloodstream infection surveillance. Arch Dis Child Fetal Neonatal Ed 2009; 94: F8-F12
• 28 Edwards MS, Baker CJ, Kaplan SL et al. Clinical features, evaluation, and diagnosis of sepsis in term and late preterm infants.: UpToDate 2016 Available from
• 29 Fairchild KD. Predictive monitoring for early detection of sepsis in neonatal ICU patients. Current opinion in pediatrics 2013; 25: 172-179
• 30 Sullivan BA, Grice SM, Lake DE. et al. Infection and other clinical correlates of abnormal heart rate characteristics in preterm infants. J Pediatr 2014; 164: 775-780
• 31 Franz AR, Kron M, Pohlandt F. et al. Comparison of procalcitonin with interleukin 8, C-reactive protein and differential white blood cell count for the early diagnosis of bacterial infections in newborn infants. The Pediatric infectious disease journal 1999; 18: 666-771
• 32 Franz AR, Steinbach G, Kron M. et al. Reduction of unnecessary antibiotic therapy in newborn infants using interleukin-8 and C-reactive protein as markers of bacterial infections. Pediatrics 1999; 104 3 Pt 1 447-453
• 33 Franz AR, Steinbach G, Kron M. et al. Interleukin-8: A valuable tool to restrict antibiotic therapy in newborn infants. Acta paediatrica (Oslo, Norway: 1992) 2001; 90: 1025-1032
• 34 Franz AR, Bauer K, Schalk A. et al. Measurement of interleukin 8 in combination with C-reactive protein reduced unnecessary antibiotic therapy in newborn infants: A multicenter, randomized, controlled trial. Pediatrics 2004; 114: 1-8
• 35 Franz AR, Sieber S, Pohlandt F. et al. Whole blood interleukin 8 and plasma interleukin 8 levels in newborn infants with suspected bacterial infection. Acta paediatrica (Oslo, Norway: 1992) 2004; 93: 648-653
• 36 Mathers NJ, Pohlandt F. Diagnostic audit of C-reactive protein in neonatal infection. European journal of pediatrics 1987; 146: 147-151
• 37 Ehl S, Gering B, Bartmann P. et al. C-reactive protein is a useful marker for guiding duration of antibiotic therapy in suspected neonatal bacterial infection. Pediatrics 1997; 99: 216-221
• 38 Benitz WE, Han MY, Madan A. et al. Serial serum C-reactive protein levels in the diagnosis of neonatal infection. Pediatrics 1998; 102: E41
• 39 Philip AG, Mills PC. Use of C-reactive protein in minimizing antibiotic exposure: Experience with infants initially admitted to a well-baby nursery. Pediatrics 2000; 106: E4
• 40 Laborada G, Rego M, Jain A. et al. Diagnostic value of cytokines and Creactive protein in the first 24 hours of neonatal sepsis. American journal of perinatology 2003; 20: 491-501
• 41 Pourcyrous M, Bada HS, Korones SB. et al. Significance of serial C-reactive protein responses in neonatal infection and other disorders. Pediatrics 1993; 92: 431-435
• 42 Orlikowsky TW, Neunhoeffer F, Goelz R. et al. Evaluation of IL-8-concentrations in plasma and lysed EDTA-blood in healthy neonates and those with suspected early onset bacterial infection. Pediatric research 2004; 56: 804-809
• 43 Buck C, Bundschu J, Gallati H. et al. Interleukin-6: A sensitive parameter for the early diagnosis of neonatal bacterial infection. Pediatrics 1994; 93: 54-58
• 44 Messer J, Eyer D, Donato L. et al. Evaluation of interleukin-6 and soluble receptors of tumor necrosis factor for early diagnosis of neonatal infection. J Pediatr 1996; 129: 574-580
• 45 Berner R, Niemeyer CM, Leititis JU. et al. Plasma levels and gene expression of granulocyte colony-stimulating factor, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-8, and soluble intercellular adhesion molecule-1 in neonatal early onset sepsis. Pediatric research 1998; 44: 469-477
• 46 Kuster H, Weiss M, Willeitner AE. et al. Interleukin-1 receptor antagonist and interleukin-6 for early diagnosis of neonatal sepsis 2 days before clinical manifestation. Lancet (London, England) 1998; 352: 1271-1277
• 47 Escobar GJ, Li DK, Armstrong MA. et al. Neonatal sepsis workups in infants>/=2000 grams at birth: A population-based study. Pediatrics 2000; 106 2 Pt 1 256-263
• 48 Chiesa C, Pellegrini G, Panero A. et al. C-reactive protein, interleukin-6, and procalcitonin in the immediate postnatal period: Influence of illness severity, risk status, antenatal and perinatal complications, and infection. Clinical chemistry 2003; 49: 60-68
• 49 Philip AG, Hewitt JR. Early diagnosis of neonatal sepsis. Pediatrics 1980; 65: 1036-1041
• 50 Russell GA, Smyth A, Cooke RW. Receiver operating characteristic curves for comparison of serial neutrophil band forms and C reactive protein in neonates at risk of infection. Arch Dis Child 1992; 67 (7 Spec No) 808-812
• 51 Doellner H, Arntzen KJ, Haereid PE. et al. Interleukin-6 concentrations in neonates evaluated for sepsis. J Pediatr 1998; 132: 295-299
• 52 Forestier F, Daffos F, Catherine N. et al. Developmental hematopoiesis in normal human fetal blood. Blood 1991; 77: 2360-2363
• 53 Walka MM, Sonntag J, Kage A. et al. Complete blood counts from umbilical cords of healthy term newborns by two automated cytometers. Acta haematologica 1998; 100: 167-173.
• 54 Segel GB, Halterman JS. Neutropenia in pediatric practice. Pediatrics in review 2008; 29: 12-23 quiz 4
• 55 Mouzinho A, Rosenfeld CR, Sanchez PJ. et al. Revised reference ranges for circulating neutrophils in very-low-birth-weight neonates. Pediatrics 1994; 94: 76-82
• 56 van der Meer W, van Gelder W, de Keijzer R. et al. Does the band cell survive the 21^st century?. European journal of haematology 2006; 76: 251-254
• 57 Newman TB, Puopolo KM, Wi S. et al. Interpreting complete blood counts soon after birth in newborns at risk for sepsis. Pediatrics 2010; 126: 903-909
• 58 Kiser C, Nawab U, McKenna K. et al. Role of guidelines on length of therapy in chorioamnionitis and neonatal sepsis. Pediatrics 2014; 133: 992-998
• 59 Newman TB, Draper D, Puopolo KM. et al. Combining immature and total neutrophil counts to predict early onset sepsis in term and late preterm newborns: Use of the I/T2. The Pediatric infectious disease journal 2014; 33: 798-802
• 60 Jackson GL, Engle WD, Sendelbach DM. et al. Are complete blood cell counts useful in the evaluation of asymptomatic neonates exposed to suspected chorioamnionitis?. Pediatrics 2004; 113: 1173-1180
• 61 Marchini G, Berggren V, Djilali-Merzoug R et al. The birth process initiates an acute phase reaction in the fetus-newborn infant. Acta paediatrica. Oslo, Norway: 1992); 2000: 89: 1082–1086
• 62 Sola MC, Del Vecchio A, Rimsza LM. Evaluation and treatment of thrombocytopenia in the neonatal intensive care unit. Clinics in perinatology 2000; 27: 655-679
• 63 Stocker M, Fontana M, El Helou S. et al. Use of procalcitonin-guided decisionmaking to shorten antibiotic therapy in suspected neonatal early-onset sepsis: Prospective randomized intervention trial. Neonatology 2010; 97: 165-174
• 64 Turner D, Hammerman C, Rudensky B. et al. Low levels of procalcitonin during episodes of necrotizing enterocolitis. Digestive diseases and sciences 2007; 52: 2972-2976
• 65 Arnon S, Litmanovitz I, Regev RH. et al. Serum amyloid A: An early and accurate marker of neonatal early-onset sepsis. Journal of perinatology: Official journal of the California Perinatal Association 2007; 27: 297-302
• 66 Schelonka RL, Maheshwari A, Carlo WA. et al. T cell cytokines and the risk of blood stream infection in extremely low birth weight infants. Cytokine 2011; 53: 249-255
• 67 Koch L, Fritzsching B, Frommhold D. et al. Lipopolysaccharide-induced expression of Th1/Th2 cytokines in whole neonatal cord and adult blood: Role of nuclear factor-kappa B and p38 MAPK. Neonatology 2011; 99: 140-145
• 68 National Collaborating Centre for Women’s and Children’s Health. National Institute for Health and Clinical Excellence: Guidance. Antibiotics for Early-Onset Neonatal Infection: Antibiotics for the Prevention and Treatment of Early-Onset Neonatal Infection. London: RCOG Press 2012
• 69 Dien Bard J, McElvania TeKippe E. Diagnosis of Bloodstream Infections in Children. Journal of clinical microbiology 2016; 54: 1418-1424
• 70 Guerti K, Devos H, Ieven MM. et al. Time to positivity of neonatal blood cultures: Fast and furious?. J Med Microbiol 2011; 60 Pt 4 446-453
• 71 Hurst MK, Yoder BA. Detection of bacteremia in young infants: Is 48 hours adequate?. The Pediatric infectious disease journal 1995; 14: 711-713
• 72 Jardine L, Davies MW, Faoagali J. Incubation time required for neonatal blood cultures to become positive. J Paediatr Child Health 2006; 42: 797-802
• 73 Vamsi SR, Bhat RY, Lewis LE. et al. Time to positivity of blood cultures in neonates. The Pediatric infectious disease journal 2014; 33: 212-214
• 74 Kumar Y, Qunibi M, Neal TJ. et al. Time to positivity of neonatal blood cultures. Arch Dis Child Fetal Neonatal Ed 2001; 85: F182-F186
• 75 Sarkar SS, Bhagat I, Bhatt-Mehta V. et al. Does maternal intrapartum antibiotic treatment prolong the incubation time required for blood cultures to become positive for infants with early-onset sepsis?. American journal of perinatology 2015; 32: 357-62
• 76 Polin RA, Watterberg K, Benitz W. et al. The conundrum of early-onset sepsis. Pediatrics 2014; 133: 1122-1123
• 77 Schelonka RL, Chai MK, Yoder BA. et al. Volume of blood required to detect common neonatal pathogens. J Pediatr 1996; 129: 275-278
• 78 KRINKO. Prävention von Infektionen, die von Gefäßkathetern ausgehen: Hinweise zur Blutkulturdiagnostik. Informativer Anhang 1 zur Empfehlung der Kommission für Krankenhaushygiene und Infektionsprävention (KRINKO) beim Robert Koch-Institut. Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz 2017; 60: 216-230
• 79 Shoji K, Komuro H, Watanabe Y. et al. The utility of anaerobic blood culture in detecting facultative anaerobic bacteremia in children. Diagnostic microbiology and infectious disease 2013; 76: 409-12
• 80 Yaacobi N, Bar-Meir M, Shchors I. et al. A prospective controlled trial of the optimal volume for neonatal blood cultures. The Pediatric infectious disease journal 2015; 34: 351-354
• 81 Patel SJ, Saiman L, Duchon JM. et al. Development of an antimicrobial stewardship intervention using a model of actionable feedback. Interdisciplinary perspectives on infectious diseases. 2012; 2012: 150367
• 82 Dunne Jr. WM, Tillman J, Havens PL. Assessing the need for anaerobic medium for the recovery of clinically significant blood culture isolates in children. The Pediatric infectious disease journal 1994; 13: 203-206
• 83 Lau YL, Hey E. Sensitivity and specificity of daily tracheal aspirate cultures in predicting organisms causing bacteremia in ventilated neonates. The Pediatric infectious disease journal 1991; 10: 290-294
• 84 KRINKO. Praktische Umsetzung sowie krankenhaushygienische und infektionspräventive Konsequenzen des mikrobiellen Kolonisationsscreenings bei intensivmedizinisch behandelten Früh- und Neugeborenen. Robert Koch-Institut, Infektionskrankheiten / Erreger 2013
• 85 Strenger V, Gschliesser T, Grisold A. et al. Orally administered colistin leads to colistin-resistant intestinal flora and fails to prevent faecal colonisation with extended-spectrum betalactamase-producing enterobacteria in hospitalised newborns. International journal of antimicrobial agents 2011; 37: 67-69
• 86 Downey LC, Benjamin Jr. DK, Clark RH. et al. Urinary tract infection concordance with positive blood and cerebrospinal fluid cultures in the neonatal intensive care unit. Journal of perinatology: Official journal of the California Perinatal Association 2013; 33: 302-306
• 87 Eldadah M, Frenkel LD, Hiatt IM. et al. Evaluation of routine lumbar punctures in newborn infants with respiratory distress syndrome. Pediatr Infect Dis J 1987; 6: 243-246
• 88 Garges HP, Moody MA, Cotten CM. et al. Neonatal meningitis: What is the correlation among cerebrospinal fluid cultures, blood cultures, and cerebrospinal fluid parameters?. Pediatrics 2006; 117: 1094-100
• 89 Smith PB, Cotten CM, Garges HP. et al. A comparison of neonatal Gram-negative rod and Gram-positive cocci meningitis. Journal of perinatology: Official journal of the California Perinatal Association 2006; 26: 111-114
• 90 Smith PB, Garges HP, Cotton CM. et al. Meningitis in preterm neonates: Importance of cerebrospinal fluid parameters. American journal of perinatology 2008; 25: 421-426
• 91 Edwards MS, Baker CJ, Kaplan SL et al. Bacterial meningitis in the neonate: Clinical features and diagnosis.: UpToDate. 2016 Available from
• 92 Malbon K, Mohan R, Nicholl R. Should a neonate with possible late onset infection always have a lumbar puncture?. Arch Dis Child 2006; 91: 75-76
• 93 Ku LC, Boggess KA, Cohen-Wolkowiez M. Bacterial meningitis in infants. Clinics in perinatology 2015; 42: 29-45 vii–viii.
• 94 Kaul V, Harish R, Ganjoo S. et al. Importance of obtaining lumbar puncture in neonates with late onset septicemia a hospital based observational study from north-west India. Journal of clinical neonatology 2013; 2: 83-87
• 95 Visser VE, Hall RT. Lumbar puncture in the evaluation of suspected neonatal sepsis. J Pediatr 1980; 96: 1063-1067
• 96 Hendricks-Munoz KD, Shapiro DL. The role of the lumbar puncture in the admission sepsis evaluation of the premature infant. Journal of perinatology: Official journal of the California Perinatal Association 1990; 10: 60-64
• 97 Stoll BJ, Hansen N, Fanaroff AA. et al. To tap or not to tap: High likelihood of meningitis without sepsis among very low birth weight infants. Pediatrics 2004; 113: 1181-1186
• 98 Flidel-Rimon O, Leibovitz E, Eventov Friedman S et al. Is lumbar puncture (LP) required in every workup for suspected late-onset sepsis in neonates? Acta paediatrica (Oslo, Norway. 1992); 2011: 100: 303–304
• 99 Greenberg RG, Benjamin Jr. DK, Cohen-Wolkowiez M. et al. Repeat lumbar punctures in infants with meningitis in the neonatal intensive care unit. Journal of perinatology: Official journal of the California Perinatal Association 2011; 31: 425-429
• 100 Heath PT, Nik Yusoff NK, Baker CJ. Neonatal meningitis. Arch Dis Child Fetal Neonatal Ed 2003; 88: F173-F178
• 101 Guilbert J, Levy C, Cohen R et al. Late and ultra late onset Streptococcus B meningitis: Clinical and bacteriological data over 6 years in France. Acta paediatrica (Oslo, Norway: 1992). 2010: 99: 47–51
• 102 Bedford H, de Louvois J, Halket S et al. Meningitis in infancy in England and Wales: Follow up at age 5 years. BMJ (Clinical research ed). 2001: 323: 533–536
• 103 Brook I. Spectrum and treatment of anaerobic infections. Journal of infection and chemotherapy: Official journal of the Japan Society of Chemotherapy 2016; 22: 1-13
• 104 de Man P, Verhoeven BA, Verbrugh HA. et al. An antibiotic policy to prevent emergence of resistant bacilli. Lancet (London, England) 2000; 355: 973-978
• 105 Le J, Nguyen T, Okamoto M. et al. Impact of empiric antibiotic use on development of infections caused by extended-spectrum beta-lactamase bacteria in a neonatal intensive care unit. The Pediatric infectious disease journal 2008; 27: 314-318
• 106 Manzoni P, Farina D, Leonessa M. et al. Risk factors for progression to invasive fungal infection in preterm neonates with fungal colonization. Pediatrics 2006; 118: 2359-2364
• 107 Polin RA. Management of neonates with suspected or proven early-onset bacterial sepsis. Pediatrics 2012; 129: 1006-1015
• 108 Clark RH, Bloom BT, Spitzer AR. et al. Empiric use of ampicillin and cefotaxime, compared with ampicillin and gentamicin, for neonates at risk for sepsis is associated with an increased risk of neonatal death. Pediatrics 2006; 117: 67-74
• 109 Muller-Pebody B, Johnson AP, Heath PT. et al. Empirical treatment of neonatal sepsis: Are the current guidelines adequate?. Arch Dis Child Fetal Neonatal Ed 2011; 96: F4-F8
• 110 Shane AL, Stoll BJ. Recent developments and current issues in the epidemiology, diagnosis, and management of bacterial and fungal neonatal sepsis. American journal of perinatology 2013; 30: 131-41.
• 111 Pfeifer Y. ESBL und AmpC: Beta-Laktamasen al seine Hauptursache der Cephalosporin-Resistenz bei Enterobakterien. Epidemiologisches Bulletin 2007; 28: 247-250
• 112 Friedman S, Shah V, Ohlsson A et al. Neonatal escherichia coli infections: Concerns regarding resistance to current therapy. Acta paediatrica (Oslo, Norway : 1992). 2000: 89: 686–689
• 113 Camacho-Gonzalez A, Spearman PW, Stoll BJ. Neonatal infectious diseases: Evaluation of neonatal sepsis. Pediatric clinics of North America 2013; 60: 367-89
• 114 Müller A, Berner R, Bartmann P. Nosokomiale Sepsis bei sehr kleinen Frühgeborenen. Monatsschr Kinderheilkd 2014; 162: 411-419
• 115 DGPI. Deutsche Gesellschaft für Pädiatrische Infektiologie e.V. DGPI Handbuch. Infektionen bei Kindern und Jugendlichen. 6^th ed Stuttgart: Georg Thieme Verlag; 2013
• 116 Yamada T, Kubota T, Nakamura M. et al. Evaluation of teicoplanin concentrations and safety analysis in neonates. International journal of antimicrobial agents 2014; 44: 458-62
• 117 Gausepohl HJ, Pöschl J. Leitfaden Neonatologie 2013. Heidelberg: Academic Press; 2013
• 118 Benjamin Jr. DK, Miller W, Garges H. et al. Bacteremia, central catheters, and neonates: When to pull the line. Pediatrics 2001; 107: 1272-1276
• 119 Jardine LA, Inglis GD, Davies MW. Prophylactic systemic antibiotics to reduce morbidity and mortality in neonates with central venous catheters. Cochrane Database Syst Rev 2008; Cd006179
• 120 O'Grady NP, Alexander M, Burns LA. et al. Guidelines for the prevention of intravascular catheter-related infections. American journal of infection control 2011; 39 (4 Suppl 1): S1-S34
• 121 Biondi EA, Mischler M, Jerardi KE. et al. Blood culture time to positivity in febrile infants with bacteremia. JAMA pediatrics 2014; 168: 844-849
• 122 Simonsen KA, Anderson-Berry AL, Delair SF. et al. Early-onset neonatal sepsis. Clinical microbiology reviews 2014; 27: 21-47
• 123 Chowdhary G, Dutta S, Narang A. Randomized controlled trial of 7-Day vs. 14-Day antibiotics for neonatal sepsis. J Trop Pediatr 2006; 52: 427-32
• 124 Hemels MA, van den Hoogen A, Verboon-Maciolek MA. et al. Shortening the antibiotic course for the treatment of neonatal coagulase-negative staphylococcal sepsis: Fine with three days?. Neonatology 2012; 101: 101-105
• 125 National Collaborating Centre for Women's and Children’s Health. National Institute for Health and Clinical Excellence: Guidance. Antibiotics for Neonatal Infection. London: RCOG Press 2014
• 126 Mukherjee A, Davidson L, Anguvaa L. et al. NICE neonatal early onset sepsis guidance: Greater consistency, but more investigations, and greater length of stay. Arch Dis Child Fetal Neonatal Ed 2015; 100: F248-F249
• 127 Palazzi DL, Klein JO, Baker CJ. Chapter 6 - Bacterial Sepsis and Meningitis. Infectious Diseases of the Fetus and Newborn Infant. 6^th ed Philadelphia: W.B. Saunders; 2006: 247-295
• 128 Patel SJ, Oshodi A, Prasad P. et al. Antibiotic use in neonatal intensive care units and adherence with Centers for Disease Control and Prevention 12 Step Campaign to Prevent Antimicrobial Resistance. The Pediatric infectious disease journal 2009; 28: 1047-1051
• 129 Lauterbach R, Zembala M. Pentoxifylline reduces plasma tumour necrosis factor-alpha concentration in premature infants with sepsis. European journal of pediatrics 1996; 155: 404-409
• 130 Lauterbach R, Pawlik D, Kowalczyk D. et al. Effect of the immunomodulating agent, pentoxifylline, in the treatment of sepsis in prematurely delivered infants: A placebo-controlled, double-blind trial. Crit Care Med 1999; 27: 807-814
• 131 Pammi M, Haque KN. Pentoxifylline for treatment of sepsis and necrotizing enterocolitis in neonates. Cochrane Database Syst Rev 2015; Cd004205
• 132 Shabaan AE, Nasef N, Shouman B. et al. Pentoxifylline therapy for late-onset sepsis in preterm infants: A randomized controlled trial. The Pediatric infectious disease journal 2015; 34: e143-e148
• 133 Carr R, Modi N, Dore C. G-CSF and GM-CSF for treating or preventing neonatal infections. Cochrane Database Syst Rev 2003; Cd003066.
• 134 Ohlsson A, Lacy JB. Intravenous immunoglobulin for suspected or proven infection in neonates. Cochrane Database Syst Rev 2015; Cd001239
• 135 Brocklehurst P, Farrell B, King A. et al. Treatment of neonatal sepsis with intravenous immune globulin. The New England journal of medicine 2011; 365: 1201-1211
• 136 He Y, Cao L, Yu J. Prophylactic lactoferrin for preventing late-onset sepsis and necrotizing enterocolitis in preterm infants: A PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore) 2018; 97: e11976
• 137 ELFIN trial investigators group. Enteral lactoferrin supplementation for very preterm infants: A randomised placebo-controlled trial. Lancet. 2019; pii: S0140-6736 18: 32221-32229 [Epub ahead of print]
• 138 Griffiths J, Jenkins P, Vargova M. et al. Enteral lactoferrin to prevent infection for very preterm infants: The ELFIN RCT. Health Technol Assess 2018; 22: 1-60
• 139 Ohlsson A, Lacy JB. Intravenous immunoglobulin for preventing infection in preterm and/or low birth weight infants. Cochrane Database Syst Rev 2013; Cd000361
• 140 Hübler A, Hummler H. Medikamentenverzeichnis. In Jorch G, Hübler A. editors Neonatologie. 1^st ed Stuttgart: Thieme Verlagsgruppe; 2010
• 141 Pineda LC, Watt KM. New antibiotic dosing in infants. Clinics in perinatology 2015; 42: 167-176 ix–x.
• 142 Young TE, Mangum B. Neofax 2009. 22^nd ed PDR Network, LLC; 2009
• 143 Reynolds LF, Mailman TL, McMillan DD. Gentamicin in neonates at risk for sepsis - peak serum concentrations are not necessary. Paediatrics & child health 2012; 17: 310-312
• 144 Tan WH, Brown N, Kelsall AW. et al. Dose regimen for vancomycin not needing serum peak levels?. Arch Dis Child Fetal Neonatal Ed 2002; 87: F214-F216