Cerebrospinal Fluid Bacterial Counts Research Articles

Developing a newborn rat model of ventriculitis without concomitant bacteremia by intraventricular injection of K1 (-) Escherichia coli.

BackgroundNeonatal meningitis caused by Escherichia coli results in high mortality and neurological disabilities, and the concomitant systemic bacteremia confounds its mortality and brain injury. This study developed an experimental model of neonatal ventriculitis without concomitant systemic bacteremia by determining the bacterial inoculum of K1 capsule‐negative E. coli by intraventricular injection in newborn rats. MethodsWe carried out intraventricular injections 1 × 102 (low dose), 5 × 102 (medium dose), or 1 × 103 (high dose) colony‐forming units (CFU) of K1 (−) E. coli (EC5ME) in Sprague‐Dawley rats at postnatal day (P) 11. Ampicillin was started at P12. Blood and cerebrospinal fluid (CSF) cultures were performed at 6 h, 1 day, and 6 days after inoculation. Brain magnetic resonance imaging (MRI) was performed at P12 and P17. Survival was monitored, and brain tissue was obtained for histological and biochemical analyses at P12 and P17. ResultsSurvival was inoculum dose‐dependent, with the lowest survival in the high‐dose group (20%) compared with the medium‐ (67%) or low‐ (73%) dose groups. CSF bacterial counts in the low‐ and medium‐dose groups were significantly lower than that in the high‐dose group at 6 h, but not at 24 h after inoculation. No bacteria were isolated from the blood throughout the experiment or from the CSF at P17. Brain MRI showed an inoculum dose‐dependent increase in the extent of brain injury and inflammatory responses. ConclusionsWe developed a newborn rat model of bacterial ventriculitis without concomitant systemic bacteremia by intraventricular injection of EC5ME.

Vancomycin versus linezolid in the treatment of methicillin-resistant Staphylococcus aureus meningitis in an experimental rabbit model

SummaryBackgroundThe aim of this study was to compare the antibacterial efficacy of vancomycin and linezolid in a rabbit model of methicillin-resistant Staphylococcus aureus (MRSA) meningitis.Material/MethodsMeningitis was induced by intracisternal inoculation of ATCC 43300 strain. After 16 h incubation time and development of meningitis, the vancomycin group received vancomycin 20 mg/kg every 12 h. The linezolid-10 and linezolid-20 groups received linezolid in 10 and 20 mg/kg dosages every 12 h, respectively. The control group did not receive any antibiotics. Cerebrospinal fluid bacterial counts were measured at the end of 16-h incubation time and at the end of 24-h treatment.ResultsBacterial counts were similar in all groups at 16 h. At the end of treatment the decrease in bacterial counts in the vancomycin group was approximately 2 logs higher than the linezolid-20 group (p>0.05) and approximately 4 logs higher than in the linezolid-10 group (p: 0.037) (Vancomycin group: −2.860±4.495 versus Linezolid-20: −0.724±4.360, versus Linezolid-10: 1.39±3.37). Full or partial bacteriological response was higher in vancomycin versus linezolid-10 (p: 0.01), but not vancomycin versus linezolid-20 or linezolid-10 versus-linezolid-20 groups.ConclusionsOur results suggest that linezolid is not statistically inferior to vancomycin in the treatment of MRSA meningitis in an experimental rabbit model in 20 mg/kg q12 h dosage; however, it is inferior in 10 mg/kg q12 h dosage. Additional data should gathered to confirm these findings in advance of clinical trials to assess efficacy in humans.

Moxifloxacin versus ampicillin + gentamicin in the therapy of experimental Listeria monocytogenes meningitis

This study aimed to compare the antibacterial activity of moxifloxacin and ampicillin + gentamicin in the treatment of Listeria monocytogenes meningitis in a rabbit meningitis model. Meningitis was induced by direct inoculation of a clinical strain isolated from an immunocompromised patient (10(7) cfu/mL) into the cisterna magna of New Zealand rabbits. After 16 h of incubation, rabbits were separated into four groups: moxifloxacin (M), ampicillin + gentamicin (A), ampicillin + gentamicin 2 (A2) and control (C). Group M received 20 mg/kg moxifloxacin at the end of the incubation time and 5 h later by intravenous (i.v.) route. Group A received ampicillin (30 mg/kg/h) and gentamicin (2.5 mg/kg/h) by i.v. route with continuous infusion for 8 h in 36 mL of 0.9% NaCl, group A2 received the same dosage of gentamicin and ampicillin in two different 36 mL 0.9% NaCl solutions and group C did not receive any treatment. Cerebrospinal fluid (CSF) samples (0.1-0.25 mL) were obtained 16 and 24 h after induction of meningitis. At the end of the 16 h of incubation, CSF bacterial counts were similar in all groups (P > 0.05). At the final stage of the study (24 h after induction of meningitis), bacterial counts in all treatment groups were significantly lower than the control group (P < 0.05). When the three treatment groups were compared, bacterial counts were found to be similar (P > 0.05). These data suggest that antibacterial activity of moxifloxacin is similar to ampicillin + gentamicin in the treatment of experimental L. monocytogenes meningitis of rabbits.

Blocking of leukocyte accumulation in the cerebrospinal fluid augments bacteremia and increases lethality in experimental pneumococcal meningitis

The role of leukocyte accumulation in the cerebrospinal fluid (CSF) in the evolution of the pathophysiological changes that occur in bacterial meningitis is unclear. Here, we investigate how leukocyte recruitment to the CSF, modulated by the leukocyte blocker fucoidin, affects the extent of brain damage and outcome in pneumococcal meningitis in rats treated with ceftriaxone from 28 h after infection. Rats treated with fucoidin from time of infection had an excess risk of a fatal outcome compared to rats not receiving fucoidin (25 / 63 versus 5 / 34, p = 0.012), whereas the risk of cortical damage in surviving animals was comparable (16 / 44 versus 9 / 29, p = 0.8). Pre-treatment with fucoidin attenuated CSF pleocytosis 24 h after infection (median 400 versus 800 × 10 6 cells/l, p = 0.01) without affecting CSF bacterial counts (2.3 × 10 5 versus 3.6 × 10 5 CFU/ml, p = 0.54). A significant increase in blood bacterial counts was found among rats pre-treated with fucoidin (median 9.6 × 10 2 versus 5.2 × 10 2 CFU/ml, p = 0.03). Furthermore, blood bacterial count was found to be an important predictor of fatal outcome as shown by multivariate logistical regression analysis (OR 4.43, 95% CI [1.16–17.0] p = 0.03). In summary, blocking leukocyte entry to the central nervous system in experimental pneumococcal meningitis compromises the survival prognosis but does not affect the risk of brain damage or level of infection in this compartment. Conversely, poorer prognosis was associated with an increase in bacterial load in blood, suggesting that leukocyte blockage affects the host's ability to control systemic infection.

Avoiding artifacts in the infant rat model for bacterial meningitis: use of Sangur test strips for the rapid quantification of blood contamination in cerebrospinal fluid.

The infant rat model is widely used to study the pathogenesis of meningitis caused by a variety of gram-positive and gram-negative bacteria. However, the interpretation of published results concerning meningitis is difficult in many records because the fact that blood contamination of the cerebrospinal fluid (CSF) cannot be avoided during the traumatic puncture procedure has not been taken into consideration. Since bacterial invasion of the central nervous system develops following bacteremia in this model, blood contamination of the CSF leads to a falsification of the CSF bacterial counts. Here we present an evaluation of a rapid and quantitative test for CSF blood contamination using Sangur test strips. The procedure requires minimal amounts of CSF and allows direct calculation of the CSF bacterial load due to blood contamination and, thus, provides refined criteria for the presence of bacterial meningitis in the infant rat model. It is superior to the detection of erythrocytes using a hemocytometer since it is less time consuming. Furthermore, we demonstrate the value of this method for the experimental infection of rats with Neisseria meningitis.

Comparison of Netilmicin with Gentamicin in the Therapy of Experimental Escherichia coli Meningitis

Netilmicin (SCH 20569), a new broad-spectrum aminoglycoside derived from sisomicin, was compared with gentamicin in the therapy of experimental Escherichia coli meningitis in rabbits. Meningitis was produced in 48 animals by the intracisternal inoculation of 10(5)E. coli colony-forming units. The minimum bactericidal concentration was 2 mug/ml against the test strain for both gentamicin and netilmicin. The two aminoglycosides demonstrated comparable penetration into the cerebrospinal fluid (CSF). The mean percent penetration [(CSF concentration/serum concentration) x 100%] was 22.5 +/- 6.0 and 20.6 +/- 7.2 for netilmicin and gentamicin, respectively (P = 0.18). However, netilmicin achieved bactericidal activity in the CSF at lower levels than did gentamicin. When mean CSF concentrations ranged from 4 to 8 mug/ml, mean CSF bacterial titers decreased 2.98 logs in rabbits treated with netilmicin but only 0.16 log in rabbits treated with gentamicin. A 2-log decrease in CSF bacterial counts was produced by a mean CSF concentration of 1.4 mug of netilmicin per ml as compared to 14.1 mug of gentamicin per ml. Because of its reduced toxicity and greater in vivo bactericidal activity, netilmicin may offer an advantage over gentamicin in the therapy of gram-negative bacillary meningitis.