Acute renal failure in the critically I11: Management by continuous veno-venous hemodiafiltration

The consequences of newer techniques of continuous renal replacement therapy in critically ill patients are not yet fully known. The clinical and biochemical impact of continuous veno-venous hemodiafiltration (CVVHD) was, therefore, prospectively studied in 60 critically ill patients with acute renal failure. Prospective clinical, biochemical, and hematological data were collected from patients receiving CVVHD. Over the initial 24 hours of therapy, CVVHD resulted in a decrease in mean plasma urea from 34.5 mmol/L (95% confidence interval [CI], 29.4 to 39.6) to 25 mmol/L (95% CI, 21.8 to 28.2). With continued CVVHD, the mean plasma urea reached a plateau level of 17.6 mmol/L (95% CI, 15.8 to 19.4) at 72 hours. This degree of azotemia control was achieved with ease and essentially without complications during 8,360 hours of therapy despite the presence of multi-organ failure and the aggressive administration of protein nitrogen (0.25 to 0.35 g/kg/day). No abnormalities of serum electrolytes developed during treatment. Survival to intensive care discharge was 46.6% and to hospital discharge 41.6%, despite a mean Acute Physiology and Chronic Health Evaluation (APACHE) Il score at presentation of 27.7. Continuous veno-venous hemodiafiltration offers superior azotemia control and a safe approach to renal replacement therapy in critically ill patients. Its use is associated with a comparatively favorable outcome. CVVHD may be regarded as the treatment of choice in such patients.     

Is Health Care Seeking for Irritable Bowel Syndrome and Functional Dyspepsia a Socially Learned Response to Illness?

In a population-based study of 207 subjects with irritable bowel syndrome (IBS) or functional dyspepsia (FD) and controls (n = 100), we aimed to determine whether dimensions of abnormal illness behavior from the Abnormal Illness Behaviour Questionnaire and aspects of social learning of illness behavior from the Social Learning of Illness Behaviour scale were independent predictors of health care seeking for IBS and FD. Results showed that dimensions of abnormal illness behavior and aspects of social learning of illness behavior (encouragement, reinforcement, and modeling) did not significantly differentiate between consulters and nonconsulters with IBS and/or FD. The Disease Conviction scale (OR = 1.55; 95% CI, 1.15–2.09) of the Abnormal Illness Behaviour Questionnaire was an independent predictor of having a diagnosis of IBS and/or FD, independent of age and gender, psychiatric diagnoses, and symptom severity. We conclude that a belief in the presence of serious pathology characterizes community subjects with IBS and FD, but not health care seeking.     

Reliability of the MS-2 system in detecting methicillin-resistant Staphylococcus aureus.

The MS-2 system (Abbott Diagnostics, Division of Abbott Laboratories, Dallas, Tex.) is an automated system capable of rapid antimicrobial susceptibility testing. However, the short incubation periods used by the device may adversely affect its ability to detect slowly growing resistant organisms. Shortly after the introduction of the MS-2 system into the University of Mississippi Medical Center clinical microbiology laboratory, we noted discrepancies between the MS-2 and the disk diffusion susceptibility reports when methicillin-resistant Staphylococcus aureus isolates were tested. Subsequently, we determined the susceptibilities of 75 such isolates by the MS-2 and Kirby-Bauer disk diffusion methods and measured the minimum inhibitory concentrations of methicillin, oxacillin, and cephalothin for 33 of the 75 isolates by standardized agar dilution techniques. There was only 47% overall agreement between the MS-2 and disk diffusion methods when methicillin was tested and 15% agreement when cephalothin was the test drug. There was 93% or more overall agreement between the two methods when other antimicrobial agents were tested. The minimum inhibitory concentration of methicillin was greater than or equal to 16 micrograms/ml for all 33 isolates evaluated by the agar dilution method. A comparison of the MS-2 and agar dilution results revealed an overall agreement of 49% when the susceptibilities to methicillin were determined. The MS-2 system reported that multiple methicillin-resistant S. aureus isolates obtained from a single patient were either resistant, intermediate, or sensitive to methicillin. Inconsistent results were also obtained when a single isolate was tested simultaneously in 10 cuvette cartridges. We conclude that the MS-2 system does not reliably detect methicillin and cephalothin resistance among S. aureus.     

Ultra-Deep Genomic Sequencing of HCV NS5A Resistance-Associated Substitutions in HCV/HIV Coinfected Patients

Background and Aims

The prevalence of naturally occurring HCV-NS5A resistance-associated substitutions (RAS) to DAA drugs might affect the response to treatment in HCV/HIV coinfected subjects. There are limited data on the frequency of HCV-NS5A naturally occurring drug-RAS at baseline in HCV/HIV coinfected patients when ultra-deep sequencing methodologies are applied.

Methods

HCV-NS5A-RAS were evaluated among 25 subjects in each group. Patients were matched by age, gender, and hepatic fibrosis stage category to control for selection bias.

Results

Within subtype 1a, RAS were observed in 28% of HCV monoinfected and 48% of HCV/HIV coinfected subjects. More patients in the HCV/HIV coinfected group had clinically relevant mutations to DAA directed at NS5A.

Conclusion

While the clinical significance of this observation may be limited in highly drug adherent populations, some HCV/HIV coinfected persons may be at greater risk of viral resistance if suboptimal dosing occurs.

     

The capsule is a virulence determinant in the pathogenesis of Pasteurella multocida M1404 (B:2)

Capsules from a range of pathogenic bacteria are key virulence determinants, and the capsule has been implicated in virulence in Pasteurella multocida. We have previously identified and determined the nucleotide sequence of the P. multocida M1404 (B:2) capsule biosynthetic locus (J. D. Boyce, J. Y. Chung, and B. Adler, Vet. Microbiol. 72:121-134, 2000). The cap locus consists of 15 genes, which can be grouped into three functional regions. Regions 1 and 3 contain genes proposed to encode proteins involved in capsule export, and region 2 contains genes proposed to encode proteins involved in polysaccharide biosynthesis. In order to construct a mutant impaired in capsule export, the final gene of region 1, cexA, was disrupted by insertion of a tetracycline resistance cassette by allelic replacement. The genotype of the tet(M) OmegacexA mutant was confirmed by Southern hybridization and PCR. The acapsular phenotype was confirmed by immunofluorescence, and the strain could be complemented and returned to capsule production by the presence of a cloned uninterrupted copy of cexA. Wild-type, mutant, and complemented strains were tested for virulence by intraperitoneal challenge of mice; the presence of the capsule was shown to be a crucial virulence determinant. Following intraperitoneal challenge of mice, the acapsular bacteria were removed efficiently from the blood, spleen, and liver, while wild-type bacteria multiplied rapidly. Acapsular bacteria were readily taken up by murine peritoneal macrophages, but wild-type bacteria were significantly resistant to phagocytosis. Both wild-type and acapsular bacteria were resistant to complement in bovine and murine serum.     

Patterns of avian seroprevalence to western equine encephalomyelitis and Saint Louis encephalitis viruses in California, USA

Temporal and spatial changes in the enzootic activity of western equine encephalomyelitis (WEE) and St. Louis encephalitis (SLE) viruses were monitored at representative wetland study sites in the Coachella, San Joaquin, and Sacramento valleys of California from 1996 to 1998 using three methods: (1) virus isolation from pools of 50 host-seeking Culex tarsalis Coquillett females, (2) seroconversions in flocks of 10 sentinel chickens, and (3) seroprevalence in wild birds collected by mist nets and grain baited traps. Overall, 74 WEE and one SLE isolates were obtained from 222,455 Cx. tarsalis females tested in 4,988 pools. In addition, 133 and 40 seroconversions were detected in 28 chicken flocks, and 143 and 27 of 20,192 sera tested from 149 species of wild birds were positive for antibodies to WEE and SLE, respectively. WEE was active in all three valleys, whereas SLE only was detected in Coachella Valley. Seroconversions in sentinel chickens provided the most sensitive indication of enzootic activity and were correlated with seroprevalence rates in wild birds. Avian seroprevalence rates did not provide an early warning of pending enzootic activity in chickens, because positive sera from after hatching year birds collected during spring most probably were the result of infections acquired during the previous season. Few seroconversions were detected among banded recaptured birds collected during spring and early summer. Age and resident status, but not sex, were significant risk factors for wild bird infection, with the highest seroprevalence rates among after hatching year individuals of permanent resident species. Migrants (with the exception of mourning doves) and winter resident species rarely were positive. House finches, house sparrows, Gambel's quail, California quail, common ground doves, and mourning doves were most frequently positive for antibodies. The initial detection of enzootic activity each summer coincided closely with the appearance of hatching year birds of these species in our study areas, perhaps indicating their role in virus amplification. Bird species most frequently positive roosted or nested in elevated upland vegetation, sites where Cx. tarsalis host-seeking females hunt most frequently. These serosurveys provided important background information for planned host competence and chronic infection studies.