APMIS 122: 654–656
© 2014 APMIS. Published by John Wiley & Sons Ltd. DOI 10.1111/apm.12219
Case Report
Fulminant neonatal sepsis due to Streptococcus alactolyticus -A case report and review NICOLE TOEPFNER,1 SINDHU SHETTY,1 MIRJAM KUNZE,2 MARZENNA ORLOWSKA-VOLK,3 4 € MARKUS KRUGER, REINHARD BERNER5 and ROLAND HENTSCHEL6 1
Clinic and Polyclinic of Pediatrics and Adolescent Medicine, Carl Gustav Carus University Hospital, Dresden; 2Department of Obstetrics and Gynecology, University Medical Center Freiburg, Freiburg; 3 Department of Pathology, University Hospital Freiburg, Freiburg; 4Centre for Pediatrics and Adolescent Medicine -Division of Neonatology/Intensive Care, University Hospital Freiburg, Freiburg; 5Clinic and Polyclinic of Pediatrics and Adolescent Medicine, Carl Gustav Carus University Hospital, Dresden; 6Centre for Pediatrics and Adolescent Medicine -Division of Neonatology/Intensive Care, University Hospital Freiburg, Freiburg, Germany
Toepfner N, Shetty S, Kunze M, Orlowska-Volk M, Kr€ uger M, Berner R, Hentschel R. Fulminant neonatal sepsis due to Streptococcus alactolyticus -A case report and review. APMIS 2014; 122: 654–656. Group D streptococci have rarely been associated with neonatal infections. We report a case of fulminant respiratory distress syndrome (RDS) caused by Streptococcus alactolyticus in a term neonate. Gram staining revealed gram-positive cocci and culture grew group D streptococci in samples taken from trachea, ear, and nasopharynx. Streptococcus alactolyticus was identified using automated microbial identification system (Vitek 2). Histopathology showed massive pulmonary inflammation with intra-alveolar granulocytosis and secondary pulmonary bleeding as etiology of fatal outcome. To our knowledge, this is first case presenting neonatal infection caused by Streptococcus alactolyticus. Key words: Streptococcus alactolyticus; neonatal sepsis; Streptococcus bovis; respiratory distress syndrome. Nicole Toepfner, Clinic and Polyclinic for Pediatrics and Adolescent Medicine, Carl Gustav Carus University, Fetscherstraße 74, 01307 Dresden, Germany. e-mail: [email protected]
Group D streptococci (GDS) are an uncommon cause of neonatal infection. S. alactolyticus was grouped under Salivarius group of Streptoccus viridans species based on phenotypic characteristics. Due to recent taxonomic changes in streptococcus genus based on gene analysis (16s rRNA), it is now included under Streptococcus bovis/Streptococcus equinus complex (1, 2). Streptococcus bovis complex is found in intestinal flora of humans and animals. Neonatal meningitis, septicemia, and chorioamnionitis due to Streptococcus gallolyticus, which belongs to S. bovis complex, have been reported (3). Since the taxonomic reorganization and subsequent update of automated microbial identification system to our knowledge, this is the first case report presenting neonatal infection caused by S. alactolyticus.
Received 8 December 2013. Accepted 29 August 2013
654
CASE PRESENTATION After an uncomplicated pregnancy and rupture of the amniotic membranes on time without any suspicion of maternal infection, a 3400 g infant was born by spontaneous delivery at 41 weeks of gestation (APGAR 31, 55, 710; umbilical cord pH = 7.30, BE: 12). After birth, sufficient oxygenation was not achieved (60–80% oxygen saturation) despite immediate suction of airway secretions, oxygen supply and mask ventilation. After tracheal intubation in the 20th life minute, positive pressure ventilation was initiated, but pressure had to be increased up to a maximum of 32 mmHg peak pressure and 10 mmHg PEEP with FiO2 of 1.0. Hemoglobin and cardiac function was normal. The first chest X-ray showed a white lung with bilateral pleural effusion. Within first hour of life, empirical antibiotic therapy with Piperacilline (200 mg/kg/day) and Tobramycin (5mg/kg/day) was initiated on suspicion of
NEONATAL SEPSIS DUE TO STREPTOCOCCUS ALACTOLYTICUS
sepsis. Tachycardia (180 bpm) and hypotension (20 mmHg mean arterial pressure) were treated with crystalloid volume replacement of 30 mL/kg. At the age of 2 h, intrapulmonary bleeding started, which could not be stopped by transfusion of thrombocytes and fresh frozen plasma. Endotracheal application of adrenaline did not show any effect on the bleeding. Prothrombin complex concentrate, fibrinogen and human immunoglobulin G were given with little effect on bleeding or respiratory distress. Temporary respiratory stabilization was achieved (FiO2 0.80) by repetitive intrapulmonary surfactant therapy. Ultimately bleeding was temporarily stopped by endotracheal application of Tranexamic acid. High frequency oscillation and nitric oxide insufflation led to short-term respiratory improvement. The severe combined respiratory and metabolic acidosis was continuously buffered with sodium bicarbonate. Circulation was stabilized with Noradrenaline (1 ug/kg/min), Adrenaline (0.8 ug/kg/min), and Hydrocortisone (1 mg/kg/ day). While the leukocyte count and the C-reactive protein (CRP) were still normal, the interleukin-6 peak was 39.715 pg/mL in the second hour of life. At the age of 12 h, a slightly elevated CRP (10 mg/ L) and a leukocytosis of 17 000 leukocytes/lL could be detected. At this time, the chest X-ray showed diffuse pulmonary infiltrates and bilateral pleural effusions. Recurrence of intrapulmonary bleeding resulted in global respiratory failure, cardiac ischemia, and death after 23 h of birth. The microscopy of the initially taken gastric fluid showed copious Gram-positive cocci. By latex agglutination (PathoDx Strep D Latex Agglutination Kit, Thermo Fisher Scientific GmbH, Ulm, Germany) cultural growth of group D-streptococci was confirmed from the tracheal fluid and the smears of ear, nose, and nasopharynx. The isolated group D streptococci were identified as S. alactolyticus by Vitek 2 (bioMerieux Vitek, Inc, Hazelwood, St. Louis, MO, USA). Blood culture and the post mortem culture of the cerebrospinal fluid as well as the histochemical tissue stainings of lung, spleen and liver tissue for fungi, bacteria, parvovirus and the screening PCR measuring highly conserved DNA sequences of bacteria revealed no other pathogens. Histopathology showed intra alveolar amniotic fluid and granulocytosis prior to pulmonary bleeding signs.
DISCUSSION Early onset sepsis (EOS) in neonates is defined as sepsis within 48–72 h or less than 7 days after birth. Group B streptococcus (GBS) is the common
© 2014 APMIS. Published by John Wiley & Sons Ltd
causative pathogen. Rarely group D streptococci (GDS) are recognized as cause for EOS. Enterococci were once classified among the group D streptococci due to the presence of group D surface antigen, but are now considered a separate genus, namely Enterococcus. S. bovis complex is considered a rare cause of neonatal infection. In adults, bacteremia and endocarditis caused by S. bovis/S. gallolyticus are associated with older age and colorectal cancer (4). Invasive infection of neonates, infants, and immunocompetent adults are rare, but recently, a longitudinal series of infantile meningitis (5), a cluster of neonatal blood stream infections (6), and a case of chorioamnionitis (7) caused by Streptococcus gallolyticus subspecies pasteurianus have been reported. These reports and reviews on neonatal infection due to S. bovis complex species suggest that its etiological role may have been underestimated due to misidentification as enterococci or viridians streptococci (8). The clinical presentation of neonatal infection due to S. bovis has been found to be similar to GBS neonatal infection. Majority of cases of bacteremia present with acute RDS and sepsis (8), as in our case. In the reported case, the prenatal GBS screening of the mother and also the neonatal GBS screening were negative. The unremarkable antenatal history and the post mortem histological findings of predominant intra-alveolar instead of interalveolar granulocytosis suggest a circumscribed peripartum onset of infection. Clear amniotic fluid aspirates and absence of meconium aspiration were observed. Therefore, a peripartal start of chorioamnionitis or a birth canal GDS transmission seems most probable. GDS colonization of the reported neonate was tested positive in all nasopharyngeal and endotracheal smears, indicating that pulmonary pathology occurred prior to systemic reaction. Based on the endotracheal isolation of S. alactolyticus, its role as causative pathogen of the respiratory distress syndrome seems to be convincing. Distinguishing GDS subspecies from enterococci, which also have group D antigen, may have therapeutic importance. Enterococcus and few viridans streptocci are resistant to cephalosporins and semisynthetic penicillins, whereas S. bovis group is sensitive to both cephalosporins and penicillin (4, 8). Moreover, the clinical course of S. bovis group infection appears to be more fulminant than that of enterococcal infection, in fact strongly resembling GBS early onset sepsis. Note worthily, the reported case was a term eutroph neonate delivered after uncomplicated pregnancy and rupture of the amniotic membranes on time without any suspicion of maternal infection. To correctly identify the
655
TOEPFNER et al.
causative pathogen in neonatal sepsis, the precise use of biochemical tests or automated microbiology identification system for subspecies identification is worthwhile for choosing appropriate antibiotic regimen and also for understanding of host–pathogen interaction and clinical correlation of distinct neonatal infection.
REFERENCES 1. Facklam R. What happened to the streptococci: overview of taxonomic and nomenclature changes. Clin Microbiol Rev 2002;15:613–630. 2. Schlegel L, Grimont F, Ageron E, Grimont PAD, Bouvet A. Reappraisal of the taxonomy of the Streptococcus bovis/Streptococcus equinus complex and related species: description of Streptococcus gallolyticus subsp. gallolyticus subsp. nov., S. gallolyticus subsp. macedonicus subsp. nov. and S. gallolyticus subsp. pasteurianus subsp. nov. Int J Syst Evol Microbiol 2003;53:631–45. 3. Nagamatsu M, Takagi T, Ohyanagi T, Yamazaki S, Nobuoka S, Takemura H, et al. Neonatal meningitis
656
4.
5.
6.
7.
8.
caused by Streptococcus gallolyticus subsp. pasteurianus. J Infect Chemother 2011;18:265–8. Abdulamir AS, Hafidh RR, Abu Bakar F. The association of Streptococcus bovis/gallolyticus with colorectal tumors: the nature and the underlying mechanisms of its etiological role. J Exp Clin Cancer Res 2011; 30:11. Klatte JM, Clarridge JE, Bratcher D, Selvarangan R. A longitudinal case series description of meningitis due to Streptococcus gallolyticus subsp. pasteurianus in infants. J Clin Microbiol 2012;50:57–60. Floret N, Bailly P, Thouverez M, Blanchot C, AlezMartin D, Menget A, et al. A cluster of bloodstream infections caused by Streptococcus gallolyticus subspecies pasteurianus that involved 5 preterm neonates in a university hospital during a 2-month period. Infect Control Hosp Epidemiol 2009;31:194–6. Steux R, Dubois D, Bonnet R, Jacquetin B, Hennequin C. Streptococcus anginosus and Streptococcus gallolyticus subsp. pasteurianus chorioamniotitis. Med Mal Infect 2008;38:507–9. Gavin PJ, Thompson RB, Horng SJ, Yogev R. Neonatal sepsis caused by Streptococcus bovis variant (biotype II/2): report of a case and review. J Clin Microbiol 2003;41:3433–5.
© 2014 APMIS. Published by John Wiley & Sons Ltd
© 2014 APMIS. Published by John Wiley & Sons Ltd. DOI 10.1111/apm.12219
Case Report
Fulminant neonatal sepsis due to Streptococcus alactolyticus -A case report and review NICOLE TOEPFNER,1 SINDHU SHETTY,1 MIRJAM KUNZE,2 MARZENNA ORLOWSKA-VOLK,3 4 € MARKUS KRUGER, REINHARD BERNER5 and ROLAND HENTSCHEL6 1
Clinic and Polyclinic of Pediatrics and Adolescent Medicine, Carl Gustav Carus University Hospital, Dresden; 2Department of Obstetrics and Gynecology, University Medical Center Freiburg, Freiburg; 3 Department of Pathology, University Hospital Freiburg, Freiburg; 4Centre for Pediatrics and Adolescent Medicine -Division of Neonatology/Intensive Care, University Hospital Freiburg, Freiburg; 5Clinic and Polyclinic of Pediatrics and Adolescent Medicine, Carl Gustav Carus University Hospital, Dresden; 6Centre for Pediatrics and Adolescent Medicine -Division of Neonatology/Intensive Care, University Hospital Freiburg, Freiburg, Germany
Toepfner N, Shetty S, Kunze M, Orlowska-Volk M, Kr€ uger M, Berner R, Hentschel R. Fulminant neonatal sepsis due to Streptococcus alactolyticus -A case report and review. APMIS 2014; 122: 654–656. Group D streptococci have rarely been associated with neonatal infections. We report a case of fulminant respiratory distress syndrome (RDS) caused by Streptococcus alactolyticus in a term neonate. Gram staining revealed gram-positive cocci and culture grew group D streptococci in samples taken from trachea, ear, and nasopharynx. Streptococcus alactolyticus was identified using automated microbial identification system (Vitek 2). Histopathology showed massive pulmonary inflammation with intra-alveolar granulocytosis and secondary pulmonary bleeding as etiology of fatal outcome. To our knowledge, this is first case presenting neonatal infection caused by Streptococcus alactolyticus. Key words: Streptococcus alactolyticus; neonatal sepsis; Streptococcus bovis; respiratory distress syndrome. Nicole Toepfner, Clinic and Polyclinic for Pediatrics and Adolescent Medicine, Carl Gustav Carus University, Fetscherstraße 74, 01307 Dresden, Germany. e-mail: [email protected]
Group D streptococci (GDS) are an uncommon cause of neonatal infection. S. alactolyticus was grouped under Salivarius group of Streptoccus viridans species based on phenotypic characteristics. Due to recent taxonomic changes in streptococcus genus based on gene analysis (16s rRNA), it is now included under Streptococcus bovis/Streptococcus equinus complex (1, 2). Streptococcus bovis complex is found in intestinal flora of humans and animals. Neonatal meningitis, septicemia, and chorioamnionitis due to Streptococcus gallolyticus, which belongs to S. bovis complex, have been reported (3). Since the taxonomic reorganization and subsequent update of automated microbial identification system to our knowledge, this is the first case report presenting neonatal infection caused by S. alactolyticus.
Received 8 December 2013. Accepted 29 August 2013
654
CASE PRESENTATION After an uncomplicated pregnancy and rupture of the amniotic membranes on time without any suspicion of maternal infection, a 3400 g infant was born by spontaneous delivery at 41 weeks of gestation (APGAR 31, 55, 710; umbilical cord pH = 7.30, BE: 12). After birth, sufficient oxygenation was not achieved (60–80% oxygen saturation) despite immediate suction of airway secretions, oxygen supply and mask ventilation. After tracheal intubation in the 20th life minute, positive pressure ventilation was initiated, but pressure had to be increased up to a maximum of 32 mmHg peak pressure and 10 mmHg PEEP with FiO2 of 1.0. Hemoglobin and cardiac function was normal. The first chest X-ray showed a white lung with bilateral pleural effusion. Within first hour of life, empirical antibiotic therapy with Piperacilline (200 mg/kg/day) and Tobramycin (5mg/kg/day) was initiated on suspicion of
NEONATAL SEPSIS DUE TO STREPTOCOCCUS ALACTOLYTICUS
sepsis. Tachycardia (180 bpm) and hypotension (20 mmHg mean arterial pressure) were treated with crystalloid volume replacement of 30 mL/kg. At the age of 2 h, intrapulmonary bleeding started, which could not be stopped by transfusion of thrombocytes and fresh frozen plasma. Endotracheal application of adrenaline did not show any effect on the bleeding. Prothrombin complex concentrate, fibrinogen and human immunoglobulin G were given with little effect on bleeding or respiratory distress. Temporary respiratory stabilization was achieved (FiO2 0.80) by repetitive intrapulmonary surfactant therapy. Ultimately bleeding was temporarily stopped by endotracheal application of Tranexamic acid. High frequency oscillation and nitric oxide insufflation led to short-term respiratory improvement. The severe combined respiratory and metabolic acidosis was continuously buffered with sodium bicarbonate. Circulation was stabilized with Noradrenaline (1 ug/kg/min), Adrenaline (0.8 ug/kg/min), and Hydrocortisone (1 mg/kg/ day). While the leukocyte count and the C-reactive protein (CRP) were still normal, the interleukin-6 peak was 39.715 pg/mL in the second hour of life. At the age of 12 h, a slightly elevated CRP (10 mg/ L) and a leukocytosis of 17 000 leukocytes/lL could be detected. At this time, the chest X-ray showed diffuse pulmonary infiltrates and bilateral pleural effusions. Recurrence of intrapulmonary bleeding resulted in global respiratory failure, cardiac ischemia, and death after 23 h of birth. The microscopy of the initially taken gastric fluid showed copious Gram-positive cocci. By latex agglutination (PathoDx Strep D Latex Agglutination Kit, Thermo Fisher Scientific GmbH, Ulm, Germany) cultural growth of group D-streptococci was confirmed from the tracheal fluid and the smears of ear, nose, and nasopharynx. The isolated group D streptococci were identified as S. alactolyticus by Vitek 2 (bioMerieux Vitek, Inc, Hazelwood, St. Louis, MO, USA). Blood culture and the post mortem culture of the cerebrospinal fluid as well as the histochemical tissue stainings of lung, spleen and liver tissue for fungi, bacteria, parvovirus and the screening PCR measuring highly conserved DNA sequences of bacteria revealed no other pathogens. Histopathology showed intra alveolar amniotic fluid and granulocytosis prior to pulmonary bleeding signs.
DISCUSSION Early onset sepsis (EOS) in neonates is defined as sepsis within 48–72 h or less than 7 days after birth. Group B streptococcus (GBS) is the common
© 2014 APMIS. Published by John Wiley & Sons Ltd
causative pathogen. Rarely group D streptococci (GDS) are recognized as cause for EOS. Enterococci were once classified among the group D streptococci due to the presence of group D surface antigen, but are now considered a separate genus, namely Enterococcus. S. bovis complex is considered a rare cause of neonatal infection. In adults, bacteremia and endocarditis caused by S. bovis/S. gallolyticus are associated with older age and colorectal cancer (4). Invasive infection of neonates, infants, and immunocompetent adults are rare, but recently, a longitudinal series of infantile meningitis (5), a cluster of neonatal blood stream infections (6), and a case of chorioamnionitis (7) caused by Streptococcus gallolyticus subspecies pasteurianus have been reported. These reports and reviews on neonatal infection due to S. bovis complex species suggest that its etiological role may have been underestimated due to misidentification as enterococci or viridians streptococci (8). The clinical presentation of neonatal infection due to S. bovis has been found to be similar to GBS neonatal infection. Majority of cases of bacteremia present with acute RDS and sepsis (8), as in our case. In the reported case, the prenatal GBS screening of the mother and also the neonatal GBS screening were negative. The unremarkable antenatal history and the post mortem histological findings of predominant intra-alveolar instead of interalveolar granulocytosis suggest a circumscribed peripartum onset of infection. Clear amniotic fluid aspirates and absence of meconium aspiration were observed. Therefore, a peripartal start of chorioamnionitis or a birth canal GDS transmission seems most probable. GDS colonization of the reported neonate was tested positive in all nasopharyngeal and endotracheal smears, indicating that pulmonary pathology occurred prior to systemic reaction. Based on the endotracheal isolation of S. alactolyticus, its role as causative pathogen of the respiratory distress syndrome seems to be convincing. Distinguishing GDS subspecies from enterococci, which also have group D antigen, may have therapeutic importance. Enterococcus and few viridans streptocci are resistant to cephalosporins and semisynthetic penicillins, whereas S. bovis group is sensitive to both cephalosporins and penicillin (4, 8). Moreover, the clinical course of S. bovis group infection appears to be more fulminant than that of enterococcal infection, in fact strongly resembling GBS early onset sepsis. Note worthily, the reported case was a term eutroph neonate delivered after uncomplicated pregnancy and rupture of the amniotic membranes on time without any suspicion of maternal infection. To correctly identify the
655
TOEPFNER et al.
causative pathogen in neonatal sepsis, the precise use of biochemical tests or automated microbiology identification system for subspecies identification is worthwhile for choosing appropriate antibiotic regimen and also for understanding of host–pathogen interaction and clinical correlation of distinct neonatal infection.
REFERENCES 1. Facklam R. What happened to the streptococci: overview of taxonomic and nomenclature changes. Clin Microbiol Rev 2002;15:613–630. 2. Schlegel L, Grimont F, Ageron E, Grimont PAD, Bouvet A. Reappraisal of the taxonomy of the Streptococcus bovis/Streptococcus equinus complex and related species: description of Streptococcus gallolyticus subsp. gallolyticus subsp. nov., S. gallolyticus subsp. macedonicus subsp. nov. and S. gallolyticus subsp. pasteurianus subsp. nov. Int J Syst Evol Microbiol 2003;53:631–45. 3. Nagamatsu M, Takagi T, Ohyanagi T, Yamazaki S, Nobuoka S, Takemura H, et al. Neonatal meningitis
656
4.
5.
6.
7.
8.
caused by Streptococcus gallolyticus subsp. pasteurianus. J Infect Chemother 2011;18:265–8. Abdulamir AS, Hafidh RR, Abu Bakar F. The association of Streptococcus bovis/gallolyticus with colorectal tumors: the nature and the underlying mechanisms of its etiological role. J Exp Clin Cancer Res 2011; 30:11. Klatte JM, Clarridge JE, Bratcher D, Selvarangan R. A longitudinal case series description of meningitis due to Streptococcus gallolyticus subsp. pasteurianus in infants. J Clin Microbiol 2012;50:57–60. Floret N, Bailly P, Thouverez M, Blanchot C, AlezMartin D, Menget A, et al. A cluster of bloodstream infections caused by Streptococcus gallolyticus subspecies pasteurianus that involved 5 preterm neonates in a university hospital during a 2-month period. Infect Control Hosp Epidemiol 2009;31:194–6. Steux R, Dubois D, Bonnet R, Jacquetin B, Hennequin C. Streptococcus anginosus and Streptococcus gallolyticus subsp. pasteurianus chorioamniotitis. Med Mal Infect 2008;38:507–9. Gavin PJ, Thompson RB, Horng SJ, Yogev R. Neonatal sepsis caused by Streptococcus bovis variant (biotype II/2): report of a case and review. J Clin Microbiol 2003;41:3433–5.
© 2014 APMIS. Published by John Wiley & Sons Ltd
