June 25, 1999
Introduction
Michael's Great Smokies lab reports of 8.7.98, 10.19.98, and 2.8.99 document intestinal colonization by Klebsiella pneumoniae (Kp) and hemolytic Eschirichia coli (hEc), which can translocate from gastrointestinal tissue into mesenteric lymph nodes, peritoneum, and other tissues, including the brain. Whether or not such translocation has occurred in Michael remains to be determined.Neurologic and other aspects of Klebsiella pneumoniae
[a] Focal neurologic deficits can occur in response to sepsis (1a), as can other CNS-related injuries (eg, 1b-f), including vascular alterations (1e), thus I wonder about a similar phenomenon in persons without sepsis but having chronic active bacterial infection in other bodily locations -- eg, blood brain barrier (1d), sinuses (2), peritonuem, and gastrointestinal tract. Some researchers imply a range of effects from gram-negative bacteria (1f), suggesting that some children might have less severe, even subclinical manifestations if the infection were sufficiently focal, perhaps even confined to vascular cells without gaining access to the CNS, which is supported by the fact that CSF is not a preferrred medium for Kp (8). [b] A canine study showed the peripheral translocation of bacteria can result in CNS involvement (3), and brain abscesses can occur in the absence of purulent meningitis (4); and "prune belly" is associated with various Klebsiella species (eg, K. oxytoca (6). [c] Predisposing conditions to Kp infections can make diagnostic imaging and treatment more problematic (5a-b); and both Kp and Ec predispose towards intra- abdominal infections (7). [d] If systemic Kp and/or hEc fragments are reaching cells of the blood-brain barrier, then vascular inflammation could be occurring (9a-b), along with associated hypoperfusion and hypofuction in adjoining brain regions and neuronal pathways connected thereto (10), as further delineated on a webpage http://www.jorsm.com/~binstock/bbb-inf.htm Teresa Binstock Researcher in Developmental and Behavioral Neuroanatomy June 25, 1999Additional report topics
Summary Why Klebsiella pneumonia and hemolytic E. coli have come to demand much attention in this report. (Kp, hEc)
Peritoneal and abdominal Kp and hEc
Neurologic aspects of Kp and hEc
Miscellany regarding Kp and hEc
A series of autism-spectrum research monographs is available by links on a web page: http://www.jorsm.com/~binstock/index.htmReferences
1a. Acta Neurol Scand 1996 Oct;94(4):279-86 Focal neurologic deficits in infective endocarditis and other septic diseases. Bitsch A, Nau R, Hilgers RA, Verheggen R, Werner G, Prange HW Department of Neurology, Georg-August University Gottingen, Germany. INTRODUCTION: Focal neurologic deficits in sepsis frequently result from parenchymal lesions due to cerebral embolism. The aim of this study was to characterize clinical, laboratory and radiologic patterns of those patients. PATIENTS AND METHODS: Medical records of 30 patients with focal neurologic symptoms during sepsis were analyzed retrospectively. RESULTS: 24 patients (22 with infective endocarditis) had ischemic stroke. Cerebrospinal fluid (CSF) analyses revealed inflammation in 11 of 12 patients. Patients who died (11/24) suffered more frequently from secondary intracerebral hemorrhage (p = 0.0031), which was significantly associated with intravenous high-dose anticoagulation (p = 0.0059). Six patients had slowly progressive focal neurologic deficits without evidence for stroke. All showed CSF inflammation and three developed multiple cerebral abscesses. CONCLUSIONS: There are two distinctive groups of patients with focal neurologic deficits during sepsis. One presents with stroke and CNS inflammation (septic embolic focal encephalitis). The other group develops slowly progressive focal neurologic deficits and sometimes multiple cerebral abscesses (septic metastatic focal encephalitis). PMID: 8937541, UI: 97091875 1b. Intern Med 1995 Jun;34(6):554-8 Magnetic resonance imaging of multiple brain abscesses of the bilateral basal ganglia. Nagase T, Wada S, Nakamura R, Morisako T, Kamakura K, Kugai N, Yamamoto M, Tsuchiya K, Nagata N Third Department of Internal Medicine, National Defense Medical College, Tokorozawa. A 64-year-old woman developed multiple brain abscesses of the basal ganglia associated with Klebsiella pneumoniae septicemia. Magnetic resonance (MR) images showed three different stages of the brain abscesses. The images of early cerebritis of this site mimicked lacunar infarctions or dilated Virchow-Robin spaces. The differentiation of the brain abscess from lacunae and dilated Virchow-Robin spaces is discussed, together with the evolution of the brain abscesses on MR images. PMID: 7549142, UI: 96012387 1c. Infection 1994 May-Jun;22(3):210-2 Ventriculitis caused by Klebsiella pneumoniae successfully treated with pefloxacin in a neonate. Linder N, Dagan R, Kuint J, Keler N, Keren G, Reichman B Dept. of Neonatology, Chaim Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel Aviv, Israel. Pefloxacin was applied to a newborn suffering from ventriculitis caused by Klebsiella pneumoniae after failure of routine antibiotics. Treatment was successful. Blood and CSF levels were high, thus documenting good CSF penetration. In addition to this case report, a review of the literature regarding seven neonates with CNS infection treated with fluoroquinolones and from whom CSF levels were obtained, is presented. In conclusion, due to their excellent activity against gram-negative microorganisms, fluoroquinolones may be considered in the treatment of neonatal CNS infections if the pathogen is resistant to routinely used antibiotics. Only limited experience is available with fluoroquinolones in pediatric patients given their potential for cartilage toxicity in young animals. Publication Types: Review Review of reported cases PMID: 7927820, UI: 95012763 1d. J Pediatr 1993 Jan;122(1):15-21 Gram-negative enteric bacillary meningitis: a twenty-one-year experience. Unhanand M, Mustafa MM, McCracken GH Jr, Nelson JD Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas. We reviewed our experience with gram-negative enteric bacillary meningitis in neonates and infants from 1969 through 1989. Ninety-eight patients were identified. Their ages were from 1 day to 2 years with a median of 10 days. In 25 patients (26%), predisposing factors were identified, the most common of which were neural tube defects and urinary tract anomalies. The causative agents were Escherichia coli (53%), Klebsiella-Enterobacter species (16%), Citrobacter diversus (9%), Salmonella species (9%), Proteus mirabilis (4%), Serratia marcescens (3%), Bacteroides fragilis (3%), and Aeromonas species (2%). At the time of diagnosis, Gram-stained smears of cerebrospinal fluid revealed gram-negative bacilli in 61% of patients. The causative organism was cultured from blood obtained from 55% of patients, and 21% had positive urine culture results. The cerebrospinal fluid leukocyte counts ranged from 0 to 80,600 cells/mm3, and the cerebrospinal fluid/serum glucose concentration ratio was less than 0.5 in 72% of patients. Antimicrobial regimens varied greatly. After initiation of antibiotic therapy, an average of 3 days was needed for eradication of bacteria from cerebrospinal fluid. The case-fatality rate was 17%, and 61% of survivors had long-term sequelae that included seizure disorders, hydrocephalus, physical disability, developmental delay, and hearing loss. PMID: 8419603, UI: 93124271 1e. AJNR Am J Neuroradiol 1994 Apr;15(4):763-5 Subcortical hemorrhage in disseminated intravascular coagulation associated with sepsis. Wijdicks EF, Silbert PL, Jack CR, Parisi JE Department of Neurology, Mayo Clinic, Rochester, MN 55905. Cranial CT features of two patients with intracerebral hemorrhages in the setting of sepsis and disseminated intravascular coagulation are reported. Multiple predominantly subcortical hemorrhages were seen. This pattern of cerebral hemorrhage should raise suspicion of disseminated intravascular coagulation as an underlying cause. PMID: 8010280, UI: 94279636 1f. Childs Nerv Syst 1992 Aug;8(5):279-80 Brain abscess in infants. Krajewski R, Stelmasiak Z Salahuddin University Hospital, Tripoli, Libya. Brain abscesses are rare in infants and their clinical presentation is specific for this age group. Seven cases of brain abscess in infants aged 2-11 months are reported. The underlying cause was meningitis in four, sepsis in two, and unknown in one. Gram-negative organisms were cultured in 6 patients. The abscess size was 5 cm or more in five cases; in four there were multiple lesions. Two abscesses were aspirated and irrigated; four particularly large lesions were drained and repeatedly aspirated and irrigated. One craniotomy was done. There were two deaths, one in the postoperative period and the other 6 months after discharge. Follow-up information is available for four children, showing a good result in only one of them. Formation of an abscess should be diagnosed early, and close ultrasound monitoring or CT scanning in infants with bacterial meningitis and sepsis is essential. The prognosis in cases in which large/multiple abscesses develop is poor. PMID: 1394267, UI: 93008052 2. Otolaryngol Head Neck Surg 1998 Oct;119(4):357-60 Sinusitis in neurologically impaired children. Brook I, Shah K Department of Pediatrics, Georgetown University, Washington, DC, USA. The microbiologic features of infected sinus aspirates in nine children with neurologic impairment were studied. Anaerobic bacteria, always mixed with aerobic and facultative bacteria, were isolated in 6 (67%) aspirates and aerobic bacteria only in 3 (33%). There were 24 bacterial isolates, 12 aerobic or facultative and 12 anaerobic. The predominant aerobic isolates were Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus (2 each) and Proteus mirabilis, Pseudomonas aeruginosa, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae (1 each). The predominant anaerobes were Prevotella sp. (5), Peptostreptococcus sp. (4), Fusobacterium nucleatum (2), and Bacteroides fragilis (1). Beta-lactamase-producing bacteria were isolated from 8 (89%) patients. Organisms similar to those recovered from the sinuses were also isolated from tracheostomy site and gastrostomy wound aspirates in five of seven instances. This study demonstrates the uniqueness of the microbiologic features of sinusitis in neurologically impaired children, in which, in addition to the organisms known to cause infection in children without neurologic impairment, facultative and anaerobic gram-negative organisms that can colonize other body sites are predominant. PMID: 9781990, UI: 98453251 3. J Am Vet Med Assoc 1996 Jan 15;208(2):243-7 Hepatic abscesses in dogs: 14 cases (1982-1994). Farrar ET, Washabau RJ, Saunders HM Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104-6010, USA. OBJECTIVES--To determine typical clinical signs and clinicopathologic findings in dogs with hepatic abscesses, to assess outcome of treatment, and to evaluate the role that abdominal ultrasonography has in the diagnosis of hepatic abscesses in dogs and in monitoring response to treatment. DESIGN--Retrospective case series. ANIMALS--14 dogs with hepatic abscesses. RESULTS--Anorexia and lethargy were the most common historical complaints, followed by vomiting and diarrhea. Physical abnormalities included fever, dehydration, signs of abdominal pain, hepatomegaly, and mucosal bleeding. Hematologic abnormalities included leukocytosis with neutrophilia, mild to moderate thrombocytopenia, and mild anemia. Serum biochemical abnormalities included high alkaline phosphatase and alanine aminotransferase activities and high bilirubin concentration; hypoalbuminemia and prolonged coagulation values were also reported. Abdominal radiography revealed hepatomegaly, poor abdominal detail, a hepatic mass, or splenomegaly in 9 dogs. Thoracic radiography revealed alveolar consolidation or mixed bronchial/interstitial pulmonary patterns in 6 dogs. Hypoechoic, heteroechoic, or hyperechoic masses were identified in all dogs in which ultrasonography was performed. Escherichia coli, Clostridium sp, Klebsiella pneumoniae, Enterococcus sp, Staphylococcus epidermidis, and S intermedius were the most common bacteria isolated from hepatic abscesses. Concurrent infections were identified in the biliary tract, spleen, blood, endocardium, lung, prostate gland, peritoneum, lymph nodes, salivary gland, or brain of several dogs. Seven dogs died or were euthanatized before definitive treatment could be initiated. One dog was successfully treated with antibiotics and was alive 12 months after medical treatment. Six dogs were treated surgically (ie, full or partial liver lobectomy, drainage, abdominal lavage) and medically (ie, antibiotic administration). Five of these dogs survived and were alive 12 months after surgery. Ultrasonography was used to monitor response to treatment in several dogs. CLINICAL IMPLICATIONS--Hepatic abscesses are rare in dogs, but the clinical signs and clinicopathologic findings are similar to other inflammatory hepatic disease. Ultrasonography revealed abnormalities in all animals in which imaging studies were performed, and was successfully used to monitor response to treatment in several dogs. Medical and surgical treatments were used successfully to treat hepatic abscesses in dogs. PMID: 8567382, UI: 96134131 4. Arch Intern Med 1991 Aug;151(8):1557-9 Septic metastatic lesions of pyogenic liver abscess. Their association with Klebsiella pneumoniae bacteremia in diabetic patients. Cheng DL, Liu YC, Yen MY, Liu CY, Wang RS Department of Medicine, Veterans General Hospital, Taipei, Taiwan, Republic of China. Septic metastatic endophthalmitis from Klebsiella pneumoniae liver abscess, first reported in seven cases treated at the Veterans General Hospital, Taipei, Taiwan, between 1981 and 1985, was seen in six similar cases at the same hospital in the subsequent 2 years. We conducted a retrospective search for factors that might be associated with these complications of pyogenic liver abscess. A total of 23 cases with septic metastatic lesions from pyogenic liver abscess were found between 1981 and 1987, and 164 cases of pyogenic liver abscess without septic metastatic lesions were identified as a comparison group. Klebsiella pneumoniae liver abscess, bacteremia, and the underlying diabetes mellitus were significantly more common in the study group than in the comparison group. Of the 23 patients with septic metastatic lesions, there were 14 cases (60.8%) of endophthalmitis or uveitis, 10 cases (43.4%) of pulmonary abscess and/or emboli, six cases (26.0%) of brain abscess and/or purulent meningitis, five cases (21.7%) of bacteriuria and/or prostate abscess, two cases (8.6%) of osteomyelitis and/or pyogenic arthritis, and one case (4.3%) of psoas abscess. PMID: 1872659, UI: 91336796 5a. AJR Am J Roentgenol 1980 Aug;135(2):263-7 CT of central nervous system infections in immunocompromised patients. Enzmann DR, Brant-Zawadzki M, Britt RH The computed tomographic (CT) scan appearance of parenchymal central nervous system (CNS) infection in 12 immunosuppressed patients was unlike that of the usual bacterial abscess in immunologically intact hosts. The lesions were poorly circumscribed and of low density. Contrast enhancement was minimal and did not assume a "ring" configuration. These CT scan findings heralded a poor prognosis. Compared to the neuropathologic findings, the CT scan generally underestimated the extent of involvement. Three other compromised patients were better able to localize the infection. This successful defense was manifested on their CT scans as the more typical "ring" pattern of contrast enhancement. Patients with this CT scan appearance of their CNS infection had a better prognosis. PMID: 6773324, UI: 80262711 5b. Pediatr Infect Dis J 1990 Nov;9(11):810-4 Cefotaxime and aminoglycoside treatment of meningitis caused by gram-negative enteric organisms. Kaplan SL, Patrick CC Myers Black Section of Pediatrics Infectious Diseases, Department of Pediatrics, Baylor College of Medicine, Houston, TX. We reviewed cases of Gram-negative enteric bacillary meningitis in infants and children treated with cefotaxime at Texas Children's Hospital from January, 1984, through June, 1989. Seventeen of 20 children had an underlying condition predisposing to the development of meningitis. The etiologic organisms in these 20 children (2 days to 12 years old; median, 12 days old) were Klebsiella sp, 9; Escherichia coli, 4; Enterobacter cloacae, 3; Citrobacter diversus, 2; other, 2. With the exception of one isolate of Acinetobacter, all isolates were susceptible to cefotaxime. In addition to cefotaxime 17 children received an aminoglycoside intravenously. Children with meningitis caused by Klebsiella sp. or non-Klebsiella organisms received cefotaxime for 31 +/- 14 and 37 +/- 17 days, respectively. Aminoglycosides were administered for 16 +/- 10 days in both groups. Five children in each group also received intraventricular doses (1 to 25) of an aminoglycoside (9) or colistimethate (1). The mean durations of positive lumbar, ventricular cerebrospinal fluid or brain abscess cultures were 5.8 +/- 4.7 and 7.2 +/- 5.0 days after start of therapy in the Klebsiella and non-Klebsiella meningitis patients, respectively. Only three children were normal at the time of discharge or follow-up. Gram-negative enteric meningitis remains difficult to treat despite the excellent in vitro activity of cefotaxime against Gram-negative enterics, in part as a result of the predisposing conditions resulting in the development of this infection. PMID: 2263430, UI: 91088226 6. Pediatr Nephrol 1998 Oct;12(8):658-9 Hyperammonaemia due to Klebsiella infection in a neuropathic bladder. Cheang HK, Rangecroft L, Plant ND, Morris AA Department of Child Health, Royal Victoria Infirmary, Newcastle upon Tyne, UK. A boy with a neuropathic bladder and a single hydronephrotic kidney developed hyperammonaemic encephalopathy during a urinary tract infection with Klebsiella oxytoca. Although particularly associated with Proteus infections and prune belly syndrome, hyperammonaemia can complicate infection with any urease-producing bacteria if there is urinary stasis. PMID: 9811390, UI: 99027529 7. Surgery 1998 Aug;124(2):418-28 Bacterially preexposed T cells impair bacterial elimination by non-Th1/Th2 cell mechanisms in a model of intra-abdominal infection. Gleason TG, Sawyer RG, Pruett TL Surgical Infectious Disease Laboratory, University of Virginia, Charlottesville 22908, USA. BACKGROUND: Escherichia coli preexposure in mice results in impaired elimination of subsequent intra-abdominal infections by a CD+4 T cell-dependent process. Certain gram-negative infections have been shown to induce T-helper-(Th)2 type CD4+ T-cell differentiation, which correlates with impaired elimination of infection and death. We hypothesized that E coli preexposure impairs subsequent bacterial elimination as a consequence of Th2 differentiation and that interleukin-12 (IL-12) treatment could reverse this differentiation and minimize the effects of E coli preexposure. METHODS: After preexposure to E coli or other species, BALB/c mice or interferon-gamma (INF-gamma)-deficient mice, treated with or without IL-12, were given a standard intra-abdominal infection (E coli, Bacteroides fragilis, and adjuvant). Cohorts were killed for abscess quantification, in vitro T-cell proliferative responsiveness, and cytokine secretory profiles. Splenic lymphocytes preexposed in vivo to other types of bacteria were transferred to naive mice before intra-abdominal infection to determine whether preexposure, eliciting the lymphocyte-dependent response, was species specific. RESULTS: E coli preexposure alone caused no Th1 or Th2 shift; increased the proliferative responses of T cells; and, in combination with IL-12 therapy, caused markedly decreased IL-2 and IL-4 responses and an increased IFN-gamma response. IL-12 therapy did not change the response to intra-abdominal infection despite its ability to cause marked Th1 polarization. IFN-gamma-deficient mice responded to E coli preexposure no differently than did wild-type mice. Transfer of lymphocytes preexposed to Pseudomonas aeruginosa, Klebsiella pneumoniae, and hemolytic E coli but not other types of nosocomial pathogens caused the development of more abscesses just as transfer of E coli preexposed lymphocytes had. CONCLUSIONS: CD4+ T cells responsive to E coli preexposure regulate subsequent intra-abdominal abscess formation by a mechanism not explained by the Th1/Th2 paradigm. Preexposure to hemolytic E coli and other Enterobacteriaceae alters responses to intra-abdominal infection. PMID: 9706167, UI: 98371424 8. Arch Neurol 1981 Jan;38(1):43-5 Effect of CSF on bacterial growth. Agbayani MM, Braun J, Chang CT, Glass L, Evans HE The growth patterns of five potentially pathogenic bacteria (Staphylococcus aureus, Escherichia coli, Listeria monocytogenes, group B beta-hemolytic streptococcus, and Klebsiella pneumoniae) and a commonly encountered, nonpathogenic microorganism (S epidermidis) were compared using CSF, trypticase soy broth (TSB), and a phosphate buffer. Each grew less in CSF than in TSB. Escherichia coli was least affected with a median difference of 2 logarithms between CSF and TSB at 24 hours of growth, whereas S epidermidis was markedly inhibited, with a median difference of 6.85 logarithms. The differences among the remaining four organisms ranged from 3.86 to 5.94 logarithms, all significantly greater than that for E. coli. Similar results were obtained at 48 hours of growth. The non-support of bacterial growth by CSF may constitute a host defense mechanism. The basis of these observations may be the presence of inhibitors or the absence of nutrients required for bacterial growth in the CSF. PMID: 6779784, UI: 81109037 9a. Infect Immun 1997 Apr;65(4):1546-9 Binding of the type 3 fimbriae of Klebsiella pneumoniae to human endothelial and urinary bladder cells. Tarkkanen AM, Virkola R, Clegg S, Korhonen TK Department of Biosciences, FIN-00014 University of Helsinki, Finland. Binding of the two identified type 3 fimbrial variants of Klebsiella pneumoniae to human endothelial EA-hy926 and bladder T24 cells was assessed. The recombinant Escherichia coli strain LE392(pFK12), expressing plasmid-encoded type 3 fimbriae of K. pneumoniae, adhered to both cell lines, and the fimbriae purified from the strain bound to both cell lines in a dose-dependent manner. Adhesiveness to both cell lines of chromosomally encoded type 3 fimbriae from K. pneumoniae IApc35 was lower. No binding was detected with type 1 fimbriae of K. pneumoniae. Both type 3 fimbrial variants exhibited a significantly lower affinity for the cell lines than did S fimbriae of meningitis-associated E. coli. PMID: 9119502, UI: 97230338 9b. Infect Immun 1995 Oct;63(10):4046-53 Activation of human endothelial cells by viable or heat-killed gram-negative bacteria requires soluble CD14. Noel RF Jr, Sato TT, Mendez C, Johnson MC, Pohlman TH Department of Surgery, University of Washington School of Medicine, Seattle 98104, USA. In response to bacterial lipopolysaccharides (LPS; endotoxin), endothelial cells are converted to an activation phenotype expressing both proinflammatory and procoagulant properties that include the induction of leukocyte adhesion molecules and tissue factor expression. LPS-induced endothelial cell activation requires a soluble form of the monocyte LPS receptor, sCD14. We evaluated the capacity of multiple strains of gram-negative and gram-positive bacteria to induce endothelial E-selectin and tissue factor expression through sCD14-dependent pathways with cultured human umbilical vein endothelial cells (HUVE). Both viable and heat-killed gram-negative bacteria (Bacteroides fragilis, Enterobacter cloacae, Haemophilus influenzae, and Klebsiella pneumoniae) but not viable or heat-killed gram-positive bacteria (Staphylococcus aureus, Enterococcus faecalis, and Streptococcus pneumoniae) induced prominent E-selectin surface expression detected by enzyme-linked immunosorbent assay. Tissue factor activity on HUVE, indicated by factor X activation, was induced in response to gram-negative bacteria but not in response to gram-positive bacteria. Gram-negative bacteria induced transcriptional activation in HUVE, indicated by the appearance of E-selectin-specific mRNA and by the demonstration of activation of NF-kappa B, a trans-activating factor necessary for E-selectin and tissue factor gene transcription. In contrast, neither E-selectin mRNA nor activation of NF-kappa B was detected in HUVE treated with gram-positive bacteria. Endothelial cell activation by gram-negative bacteria in each of these assays was inhibited with a monoclonal antibody (60bd) against CD14. Furthermore, CHO-K1 cells, transfected with human recombinant CD14, responded to all strains of gram-negative bacteria (viable or heat killed), indicated by CHO-K1 NF-kappa B activation. We conclude that gram-negative bacteria induce endothelial cell activation through a common sCD14-dependent pathway. PMID: 7558318, UI: 96009765 10. A preliminary analysis of bbb infections and sequalae therefrom HTTP://www.jorsm.com/~binstock/bbb-inf.htm