Do specific virus-bacteria pairings drive clinical outcomes of pneumonia?

Bacterial pneumonia is a common contributor to severe outcomes of influenza. Epidemiological data suggest that the incidence, severity and associated bacterial pathogens differ between epidemics and by geographical location within epidemics. Data from animal models demonstrate that differences in both viral and bacterial strains alter the incidence and outcomes of pneumonia. For influenza viruses, evolutionary changes to specific virulence factors appear to alter the ability of viruses within particular lineages to prime the host for secondary bacterial infection. Although bacterial strains differ considerably in disease potential in the setting of viral co-infection, the bacterial virulence factors underlying this finding are currently unknown. The hypothesis that geographical variation exists in the prevalence of bacterial strains expressing factors that enable efficient disease potentiation during viral epidemics should be considered as one explanation for regional differences in severity. This would have implications for surveillance, vaccine development, and the conduct of clinical trials for the prevention or treatment of pneumonia.

Association between tea ingestion and invasive Bacillus cereus infection among children with cancer.

Bacillus cereus is an emerging pathogen that causes invasive disease in immunocompromised hosts. A case-control study, prompted by a clinical case, demonstrated an association between dietary tea ingestion and B. cereus bacteremia. Policies designed to interrupt transmission of this pathogen to susceptible patients should be considered.

Pneumococcal meningitis in children: relationship of antibiotic resistance to clinical characteristics and outcomes.

BACKGROUND: The relationship of antibiotic susceptibility to clinical outcome in children with pneumococcal meningitis is uncertain. Previous studies have been limited by inclusion of relatively few patients infected with nonsusceptible pneumococci and inconsistent use of empiric vancomycin. METHODS: Medical records of 86 children with culture-confirmed pneumococcal meningitis at a single institution from October, 1991, to October, 1999, were retrospectively reviewed, and differences in presentation and outcome based on antibiotic susceptibility of pneumococcal isolates were assessed. RESULTS: Of 86 isolates 34 were nonsusceptible to penicillin (12 resistant). Of 60 isolates for which cefotaxime susceptibility data were available, 17 were nonsusceptible (12 resistant). Antibiotic susceptibility was not significantly associated with death, intensive care unit admission, mechanical ventilation, focal neurologic deficits, seizures, secondary fever, abnormal neuroimaging studies or hospital days. Children with penicillin-resistant isolates had significantly higher median blood leukocyte counts (24,100/microliter vs. 15,700/microliter, P = 0.03) and lower median CSF protein concentrations (85 mg/dl vs. 219 mg/dl, P = 0.04), were more likely to have a CSF glucose concentration of > or = 50 mg/dl (7 of 11 vs. 15 of 68, P = 0.009) and had lower rates of sensorineural hearing loss (1 of 8 vs. 25 of 40, P = 0.02) than children with isolates that were not resistant to penicillin. Children with cefotaxime-nonsusceptible isolates had an increased median duration of primary fever compared with those with nonsusceptible strains (6 days vs. 3.5 days, P = 0.02). CONCLUSIONS: In children with pneumococcal meningitis, penicillin resistance was associated with a reduced risk of hearing loss, while cefotaxime resistance was associated with a longer duration of fever. Other outcome measures were not significantly influenced by the antibiotic susceptibility of pneumococcal isolates.

Molecular pathogenesis of pneumococcal pneumonia.

The past two decades have witnessed an explosion of data on the molecular pathogenesis of pneumonia caused by Streptococcus pneumoniae, one of the most important pathogens currently plaguing man. Identification and functional analysis of genes and their proteins, elucidation of mechanisms involved in adherence, colonization, inflammation, and invasion, and an understanding of interactions with the host and with external factors have provided knowledge that can be used to attack this organism with small molecule or vaccine based strategies. Study of the pneumococcus has also led to insights into other pathogens that share a unique spectrum of respiratory disease. In this review we will discuss recent advances in our understanding of the pathogenesis of pneumonia due to S. pneumoniae, highlighting emerging themes common to other organisms such as Haemophilus influenzae and Neisseria meningitidis.

Bacillus cereus bacteremia and meningitis in immunocompromised children.

Two cases of Bacillus cereus meningitis in immunocompromised children at our hospital within a 2-month period prompted us to review B. cereus--related invasive disease. We identified 12 patients with B. cereus isolated in blood cultures from September 1988 through August 2000 at our institution. Three of these patients also had B. cereus isolated from CSF specimens; 1 additional patient had possible CNS involvement (33%, group A), whereas 8 patients had no evidence of CNS involvement (67%, group B). Patients in group A were more likely to have neutropenia at the onset of sepsis and were more likely to have an unfavorable outcome. They were also more likely to have received intrathecal chemotherapy in the week before the onset of their illness. Two patients from group A died. One survived with severe sequelae. The fourth patient had mild sequelae at follow-up. No sequelae or deaths occurred among patients in group B. In patients with unfavorable outcomes, the interval from the time of recognition of illness to irreversible damage or death was short, which demonstrates a need for increased awareness, early diagnosis, and more-effective therapy, particularly that which addresses B. cereus toxins.

Candidal meningitis in children with cancer.

Candidal meningitis is a rare disease that is seen most frequently in neonates, neurosurgical patients, and the immunocompromised host. We describe a series of 12 children with cancer (all of whom had leukemia) who had candidal meningitis develop. Univariate analysis revealed that duration of fever, antibiotic therapy, and profound neutropenia and use of total parenteral nutrition were significantly associated (P<.05) with candidal meningitis in children with cancer, compared with matched control subjects. Only duration of profound neutropenia (P=.08) and use of total parenteral nutrition (P=.06) approached significance in the multivariate analysis. One species of Candida, Candida tropicalis, was responsible for 11 of the 12 cases, indicating increased pathogenicity of this organism in CNS disease. The cases were invariably fatal, supporting aggressive treatment of candidal meningitis in immunocompromised patients and further study of the prevention, diagnosis, and management of C. tropicalis meningitis.

Isolation and characterization of vancomycin-tolerant Streptococcus pneumoniae from the cerebrospinal fluid of a patient who developed recrudescent meningitis.

The emergence of tolerance to vancomycin has recently been reported in Streptococcus pneumoniae, the most common cause of bacterial meningitis. A vancomycin- and cephalosporin-tolerant strain of S. pneumoniae, the Tupelo strain, was isolated from the cerebrospinal fluid of a patient who then developed recrudescence of meningitis despite treatment with vancomycin and a third-generation cephalosporin. The Tupelo strain evidenced no lysis in the exponential or stationary phase of growth when exposed to vancomycin and only minimal loss of viability. Further characterization revealed normal autolysin expression, localization, and triggering by detergents, indicating that the defect leading to tolerance in the Tupelo strain is in the control pathway for triggering of autolysis. Because tolerance is a precursor phenotype to resistance and may lead to clinical failure of antibiotic therapy, these observations may have important implications for vancomycin use in infections caused by S. pneumoniae.

Reassortment and insertion-deletion are strategies for the evolution of influenza B viruses in nature.

The evolution of influenza B viruses is poorly understood. Reassortment of influenza B viruses in nature as a means of genetic variation has not been considered to be a major contributor to their evolution. However, the current practice of assigning evolutionary relationships by antigenic analysis of the hemagglutinin of influenza B viruses would fail to detect reassortants. In this study, influenza B viruses isolated within the past 10 years from sites in the United States and China were studied by nucleotide sequencing of the hemagglutinin and neuraminidase genes and construction of phylogenetic trees to assess evolutionary relationships. A group of viruses represented by B/Houston/1/92 possess a hemagglutinin derived from a B/Yamagata/16/88-like strain and a neuraminidase derived from a B/Victoria/2/87-like strain. A second reassortment event between the hemagglutinin of a B/Yamagata/16/88-like virus closely related to the B/Beijing/184/93 strain and the neuraminidase of a B/Victoria/2/87-like strain is represented by a single virus, B/Memphis/3/93. The neuraminidase of the reassortant viruses is most closely related to that of B/Victoria/2/87-like viruses currently circulating in Nanchang, China. A pattern of insertions and deletions in the hemagglutinin and the neuraminidase of different strains of influenza B viruses is observed. Reassortment plays a role in the evolution of influenza B viruses and may necessitate a change in the methods used to assess and identify new influenza viruses.

Influenza B virus encephalitis.

Acute encephalitis and postinfectious encephalopathy have been reported infrequently in association with influenza A and B virus infections. We report herein a case of a 6-year-old girl with acute influenza B virus encephalitis resulting in neurological sequelae. The diagnosis was made by isolation of influenza B virus from the nasopharynx, seroconversion to influenza B, and reverse transcription polymerase chain reaction (RT-PCR) identification of the virus from the patient's cerebrospinal fluid. Direct sequencing of viral RNA from the patient's nasopharynx and cerebrospinal fluid revealed identical nucleotide sequences in the HA1 region of the hemagglutinin gene. This is the first report of influenza B virus encephalitis diagnosed by use of RT-PCR and illustrates the need for increased awareness of influenza virus as a cause of acute encephalitis. PCR may be a useful tool for diagnosing future cases.

Characterization of influenza A/HongKong/156/97 (H5N1) virus in a mouse model and protective effect of zanamivir on H5N1 infection in mice.

A recent outbreak of influenza in Hong Kong was caused by a highly virulent virus of avian origin. Concern that the appearance of such a virus in the human population may be a harbinger of a new pandemic has brought increased attention to the issue of antivirals available for treatment of influenza. A/HongKong/156/97 (H5N1), the first virus of H5N1 subtype isolated from a human host, is highly virulent in the mouse model and can infect mouse lungs without requiring adaptation. High mortality and evidence of systemic disease, including spread to the brain after intranasal inoculation, are observed. Zanamivir, a novel neuraminidase inhibitor, is effective at decreasing replication of the virus in vitro. In a model of lethal challenge in mice, zanamivir reduces lung titers of the virus and decreases morbidity and mortality.

Human herpesvirus 6 is associated with focal encephalitis.

Human herpesvirus 6 (HHV-6) is a cause of roseola infantum. Recent reports associate HHV-6 with cases of encephalitis; however, conclusive etiologic data do not exist. We evaluated clinical data and laboratory specimens obtained from patients with focal encephalitis of unknown etiology. Cerebrospinal fluid (CSF) specimens were tested by polymerase chain reaction for the presence of HHV-6 DNA. Selected samples were analyzed by DNA sequencing. We detected HHV-6 DNA in the CSF of nine of 138 patients. DNA sequencing revealed that group B strains of HHV-6 were present in those specimens that were analyzed. No significant differences could be demonstrated in clinical presentation, laboratory findings, or neurodiagnostic imaging results between the nine patients with confirmed HHV-6 infection and the 129 patients without evidence of HHV-6 infection. Neurological outcome for the nine HHV-6-infected patients varied from complete recovery without neurological deficit to death. Further prospective study is warranted.