The impact of converting to a biphasic blood-culture system on the overall cost and the incidence of pseudobacteremia.

After converting from a conventional broth (CB) system to a biphasic (BP) agar-slide blood-culture system (Septi-Chek), our laboratory noted an increase in positive blood cultures in general, and in coagulase-negative staphylococci (CNS) in particular. To investigate these findings, we compared all blood cultures collected over a 21-month period using CB and then BP systems, totaling 28,199 blood cultures. The frequency of positive blood cultures increased from 9.2% to 12.7% (p less than 0.0001), whereas CNS isolation increased from 2.6% to 5.2% (p less than 0.0001). There was no significant change in the incidence of true primary or secondary bacteremia due to CNS (p = 0.9). The isolation of other pathogens, including Staphylococcus aureus, Candida albicans, Bacteroides species, and Gram-negative bacilli increased from 6.5% to 7.1% (p less than 0.05). We estimated the cost of processing 28,000 blood cultures by both CB and BP systems, using positivity rates of 9.2% and 12.7%, respectively, and standards provided by the College of American Pathologists (CAP, 1991) for workload hours of technologist time. We calculated a higher overall cost for the BP system. However, the use of this system eliminated the use of needles and syringes for subculture of bottles showing no growth, thus decreasing the risk of technologist exposure to body fluids. Despite the increased cost and more frequent occurrence of pseudobacteremia, the enhanced sensitivity and increased safety of the BP system justified its use in the prompt identification of patients with true bacteremia.     

Analysis of an outbreak of penicillinase-producing Neisseria gonorrhoeae in Rhode Island, 1987.

In June of 1987, an outbreak of penicillinase-producing Neisseria gonorrhoeae (PPNG) occurred in Rhode Island. PPNG persists as an endemic pathogen despite a concerted statewide effort to eradicate the organism. Detailed analysis of PPNG isolates demonstrated that multiple strains are circulating concurrently, complicating control measures.     

Antibacterial therapy in patients with malignancies

Summary Patients with malignant disease may be predisposed to bacterial infections because of neoplastic disruption of normal tissue barriers, exogenous immunosuppressive therapy (drugs with or without radiation), and intrinsic host immune deficits secondary to these diseases. Diminished polymorphonuclear leukocyte numbers or function and impaired humoral immunity are highly correlated with the development of serious bacterial infections. The usual signs and symptoms of infection may be absent or altered in a compromised host.Therapy must be instituted promptly upon clinical suspicion of bacterial infection, and empirical choices should usually include combinations that are synergistic for likely pathogens based on knowledge of the local predominant flora and susceptibility data. Synergism has most often been demonstrated in combinations that utilize a -lactam (semisynthetic penicillin or cephalosporin) and an aminoglycoside. Triple drug therapy has not been shown to be advantageous. Monotherapy with third generation cephalosporins, carbapenems, monobactams, or ureidopenicillins has not been proven to offer advantages over 2-drug regimens for these patients.Patients with blood deficient in granulocytes (granulocytopenic) who respond to 2-drug therapy but remain deficient in neutrophils (neutropenic) may need continued treatment until the neutropenia subsides. Those who do not respond and remain febrile with an unclear focus of infection may need to be started on antifungal therapy in addition to the antibacterial agent. The use of oral agents for the prophylaxis of neutropenic patients against bacteremia remains controversial. If drugs are used, co-trimoxazole and nystatin suspension may be preferable.     

Spontaneous bacterial peritonitis: Analysis of treatment and outcome

Spontaneous bacterial peritonitis occurred on 44 separate occasions in 43 patients during a five year period, including 27 culture positive and 17 probable cases of spontaneous bacterial peritonitis. Alcoholic liver disease was the underlying cause of 72% of cases. Of the 27 culture positive cases, Escherichia coli was the most common isolate (14 cases), followed by Klebsiella pneumoniae (three cases), group G streptococci (three cases), group B streptococci (two cases) and one case each of five other organisms. Bacteremia occurred in 50% of cases and was the same as the peritoneal isolate 88% of the time. The overall mortality rate was 65% (66% culture positive and 60% probable spontaneous bacterial peritonitis). The mean interval between onset of symptoms and death was 10.2±8.6 days in fatal cases. Spontaneous bacterial peritonitis was felt to be a contributing cause of mortality in 70% of fatal cases. Survivors were younger (44±20 years versus 59±13, P<0.05) and less likely to develop renal insufficiency than nonsurvivors (38% versus 73%, P<0.05). Patients who were treated with an aminoglycoside were more likely to develop renal failure compared to those treated with nonaminoglycoside regimens (P<0.05). There was no difference in mortality rate between culture positive and culture negative spontaneous bacterial peritonitis, total peritoneal leukocyte counts, Gram-positive versus Gram-negative organisms, presence of bacteremia, or serum albumin or bilirubin levels. The mortality rate for this disease remains unacceptably high, indicating a need for the development of new strategies in the prevention, diagnosis and management of this disease.     

Active immunization with a detoxified endotoxin vaccine protects against lethal polymicrobial sepsis: its use with CpG adjuvant and potential mechanisms

BACKGROUND: An experimental vaccine for sepsis, composed of detoxified Escherichia coli J5 lipopolysaccharide (LPS) complexed with the outer membrane protein (OMP) of Neisseria meningitidis group B, induces anti-core glycolipid antibody and has been tested in pilot studies in human volunteers. METHODS: Mice were immunized with the LPS-J5/OMP vaccine with or without synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs as a vaccine adjuvant (CpG ODN). The efficacy of the vaccine-induced antibody response was tested in a cecal ligation and puncture model. RESULTS: Immunization resulted in a >20-fold increase in anti-core glycolipid antibody levels, which were further increased 5-fold by the addition of CpG ODN, compared with the levels in mice in the control group. The vaccine provided a survival advantage after a cecal ligation and puncture was performed (P < .01) and significantly decreased the levels of bacteria in organs. Immunoglobulin G (IgG) anti-core glycolipid antibodies were decreased in mice to a significantly greater extent than were levels of total circulating IgG or IgG to the OMP part of the vaccine complex, suggesting specific epitope binding and clearance. CONCLUSIONS: These results indicate that the detoxified LPS-J5/OMP vaccine induces high levels of antibody against the core glycolipid of LPS and functions in vivo to promote clearance of gram-negative bacteria and improve the outcome of experimental polymicrobial intra-abdominal sepsis.     

The estrous cycle modulates rat caudate–putamen medium spiny neuron physiology

The neuroendocrine environment in which the brain operates is both dynamic and differs by sex. How differences in neuroendocrine state affect neuron properties has been significantly neglected in neuroscience research. Behavioral data across humans and rodents indicate that natural cyclical changes in steroid sex hormone production affect sensorimotor and cognitive behaviors in both normal and pathological contexts. These behaviors are critically mediated by the caudate–putamen. In the caudate–putamen, medium spiny neurons (MSNs) are the predominant and primary output neurons. MSNs express membrane‐associated estrogen receptors and demonstrate estrogen sensitivity. However, how the cyclical hormone changes across the estrous cycle may modulate caudate–putamen MSN electrophysiological properties remains unknown. Here, we performed whole‐cell patch‐clamp recordings on male, diestrus female, proestrus female, and estrus female caudate–putamen MSNs. Action potential, passive membrane, and miniature excitatory post‐synaptic current properties were assessed. Numerous MSN electrical properties robustly differed by cycle state, including resting membrane potential, rheobase, action potential threshold, maximum evoked action potential firing rate, and inward rectification. Strikingly, when considered independent of estrous cycle phase, all but one of these properties do not significantly differ from male MSNs. These data indicate that female caudate–putamen MSNs are sensitive to the estrous cycle, and more broadly, the importance of considering neuroendocrine state in studies of neuron physiology.     

Toll‐like receptor 4 differentially regulates adult hippocampal neurogenesis in an age‐ and sex‐dependent manner

Toll‐like receptor 4 (TLR4) is primarily responsible for initiating an immune response following pathogen recognition. However, TLR4 is also expressed on neural progenitor cells and has been reported to regulate hippocampal neurogenesis as young male TLR4 knockout mice show increases in cell proliferation and doublecortin positive cells. Whether these effects occur in both sexes and are sustained with normal aging is currently unknown. The present study evaluated whether TLR4 deficiency alters adult hippocampal neurogenesis in young (3–4 months) and aged (18–20 months), male and female, TLR4 deficient (TLR4?/?; B6.B10ScN‐Tlr4lps‐del/JthJ) and wild type (WT) mice. Additionally, neurogenesis within the dorsal and the ventral hippocampal subdivisions was evaluated to determine if TLR4 has differential effects across the hippocampus. Bromodeoxyuridine (BrdU) was administered to quantify new cell survival as well as cell differentiation. Ki‐67 was measured to evaluate cell proliferation. Results show that young TLR4?/? females had higher rates of proliferation and neuronal differentiation in both the dorsal and ventral hippocampus relative to WT females. Young TLR4?/? males show elevated proliferation and neuronal differentiation mainly in the ventral hippocampus. While young TLR4?/? mice show enhanced neurogenesis compared to young WT mice, the increase was not apparent in the aged TLR4?/? mice. Both aged WT and TLR4?/? mice showed a decrease in proliferation, new cell survival, and neuronal differentiation compared to young WT and TLR4?/? mice. The data collectively indicate that TLR4 regulates hippocampal neurogenesis in young adults, but that these effects are region‐specific in males and that females show broader changes in neurogenesis throughout the hippocampus.     

Distress of ostracism: oxytocin receptor gene polymorphism confers sensitivity to social exclusion

A single-nucleotide polymorphism on the oxytocin receptor gene (OXTR), rs53576, involving a guanine (G) to adenine (A) substitution has been associated with altered prosocial features. Specifically, individuals with the GG genotype (i.e. the absence of the polymorphism) display beneficial traits including enhanced trust, empathy and self-esteem. However, because G carriers might also be more socially sensitive, this may render them more vulnerable to the adverse effects of a negative social stressor. The current investigation, conducted among 128 white female undergraduate students, demonstrated that relative to individuals with AA genotype, G carriers were more emotionally sensitive (lower self-esteem) in response to social ostracism promoted through an on-line ball tossing game (Cyberball). Furthermore, GG individuals also exhibited altered blood pressure and cortisol levels following rejection, effects not apparent among A carriers. The data support the view that the presence of the G allele not only promotes prosocial behaviors but also favors sensitivity to a negative social stressor.