Joseph R. Thurn

d-lactate encephalopathy

Although D-lactate is not a product of human intermediary metabolism, absorption of D-lactate produced by abnormal intestinal bacteria can cause systemic acidosis in patients who have undergone gastrointestinal surgery, particularly jejunoileal bypass. In order to learn more about the prevalence of D-lactate encephalopathy, its occurrence in other disorders, and how well D-lactate concentration correlates with clinical symptoms, serum D-lactate levels were determined in several specific populations. D-lactate was undetectable (less than 0.5 mmol/liter) in 72 healthy volunteers and 57 obese persons. In 33 patients who had jejunoileal bypass, 16 reported symptoms consistent with D-lactate encephalopathy since surgery. Nine of these 16 had D-lactate levels greater than 0.5 mmol/liter (range 0.7 to 11.5 mmol/liter). Levels of D-lactate fluctuated over time, and in two patients, markedly elevated levels correlated with an encephalopathy accompanied by hyperchloremic metabolic acidosis and elevated anion gap. In 470 randomly chosen hospitalized patients, D-lactate level greater than 0.5 mmol/liter was found in 13 (2.8 percent), and 60 percent of these had a history of gastrointestinal surgery or disease. It is concluded that elevated serum D-lactate levels are relatively common in patients with jejunoileal bypass, and although more rare, occur in other gastrointestinal disorders as well. The symptoms of D-lactate encephalopathy are quite sensitive, but not necessarily specific for this disorder.

Molecular Analysis of a Hospital Cafeteria-Associated Salmonellosis Outbreak Using Modified Repetitive Element PCR Fingerprinting

ABSTRACT A hospital cafeteria-associated outbreak of gastroenteritis due toSalmonella enterica serotype Infantis was retrospectively evaluated using modified repetitive element PCR (rep-PCR) fingerprinting with the ERIC2 and BOXA1R primers and computer-assisted gel analysis and dendrogram construction. Rep-PCR yielded objective between-cycler, same-strain similarity values of from 92% (composite fingerprints) to 96% (ERIC2 fingerprints). The 70Salmonella isolates (which included 19 serotype Infantis isolates from the hospital outbreak, 10 other serotype Infantis isolates, and 41 isolates representing 14 other serotypes) were resolved well to the serotype level with each of the three fingerprint types (ERIC2, BOXA1R, and composite). Rep-PCR typing uncovered several historical serotyping errors and provided presumptive serotype assignments for other isolates with incomplete or undetermined serotypes. Analysis of replicate fingerprints for each isolate, as generated on two different thermal cyclers, indicated that most of the seeming subserotype discrimination noted in single-cycler dendrograms actually represented assay variability, since it was not reproducible in combined-cycler dendrograms. Rep-PCR typing, which would have been able to identify the presence of the hospital-associated serotype Infantis outbreak after the second outbreak isolate, could be used as a simple surrogate for serotyping by clinical microbiology laboratories that are equipped for diagnostic PCR.

Preventing central venous catheter-associated primary bloodstream infections: characteristics of practices among hospitals participating in the Evaluation of Processes and Indicators in Infection Control (EPIC) study.

OBJECTIVES To describe the conceptual framework and methodology of the Evaluation of Processes and Indicators in Infection Control (EPIC) study and present results of CVC insertion characteristics and organizational practices for preventing BSIs. The goal of the EPIC study was to evaluate relationships among processes of care, organizational characteristics, and the outcome of BSI. DESIGN This was a multicenter prospective observational study of variation in hospital practices related to preventing CVC-associated BSIs. Process of care information (eg, barrier use during insertions and experience of the inserting practitioner) was collected for a random sample of approximately 5 CVC insertions per month per hospital during November 1998 to December 1999. Organization demographic and practice information (eg, surveillance activities and staff and ICU nurse staffing levels) was also collected. SETTING Medical, surgical, or medical-surgical ICUs from 55 hospitals (41 U.S. and 14 international sites). PARTICIPANTS Process information was obtained for 3,320 CVC insertions with an average of 58.2 (+/- 16.1) insertions per hospital. Fifty-four hospitals provided policy and practice information. RESULTS Staff spent an average of 13 hours per week in study ICU surveillance. Most patients received nontunneled, multiple lumen CVCs, of which fewer than 25% were coated with antimicrobial material. Regarding barriers, most clinicians wore masks (81.5%) and gowns (76.8%); 58.1% used large drapes. Few hospitals (18.1%) used an intravenous team to manage ICU CVCs. CONCLUSIONS Substantial variation exists in CVC insertion practice and BSI prevention activities. Understanding which practices have the greatest impact on BSI rates can help hospitals better target improvement interventions.

Methicillin-resistant Staphylococcus aureus in Minnesota nursing homes

Objective: To assess the experience of Minnesota nursing homes with methicillin‐resistant Staphylococcus aureus (MRSA) and the policies and procedures used for its control.

Human immunodeficiency virus type 1 and mucosal humoral defense.

Mucosal sites serve as the principle venues through which primary human immunodeficiency virus type 1 (HIV-1) infections are transferred from donor to host. These moist tissues, which provide the interface with the external environment, also provide access to many of the secondary opportunistic infections that aggravate and may accelerate HIV-1 disease. Antibodies to HIV-1, particularly of the IgG rather than the IgA class, have been detected in virtually all mucosal fluids from HIV-1-infected patients. However, the ability of such patients to generate de novo humoral responses to new mucosal pathogens is impaired. Current studies are directed to characterizing the functional role of natural and infection-derived antibodies in control of HIV-1 infection as well as the impact of HIV-1 disease on mucosal B cell responses to immunization and infection.

Use of a Computer Decision Support System and Antimicrobial Therapy Appropriateness

OBJECTIVE  To determine whether antimicrobial (AM) courses ordered with an antimicrobial computer decision support system (CDSS) were more likely to be appropriate than courses ordered without the CDSS. DESIGN  Retrospective cohort study. Blinded expert reviewers judged whether AM courses were appropriate, considering drug selection, route, dose, and duration. SETTING  A 279-bed university-affiliated Department of Veterans Affairs (VA) hospital. PATIENTS  A 500-patient random sample of inpatients who received a therapeutic AM course between October 2007 and September 2008. Intervention. An optional CDSS, available at the point of order entry in the VA computerized patient record system. RESULTS CDSS courses were significantly more likely to be appropriate (111/254, 44%) compared with non-CDSS courses (81/246, 33%, P = .013). Courses were more likely to be appropriate when the initial provider diagnosis of the condition being treated was correct (168/273, 62%) than when it was incorrect, uncertain, or a sign or symptom rather than a disease (24/227, 11%, P < .001. In multivariable analysis, CDSS-ordered courses were more likely to be appropriate than non-CDSS-ordered courses (odds ratio [OR], 1.83; 95% confidence interval [CI], 1.13-2.98). Courses were also more likely to be judged appropriate when the initial provider diagnosis of the condition being treated was correct than when it was incorrect, uncertain, or a sign or symptom rather than a disease (OR, 3.56; 95% CI, 1.4-9.0). CONCLUSIONS  Use of the CDSS was associated with more appropriate AM use. To achieve greater improvements, strategies are needed to improve provider diagnoses of syndromes that are infectious or possibly infectious.

Decreased Mutation Frequencies among Immunoglobulin G Variable Region Genes during Viremic HIV-1 Infection

Background/objective HIV-1 infection is complicated by high rates of opportunistic infections against which specific antibodies contribute to immune defense. Antibody function depends on somatic hypermutation (SHM) of variable regions of immunoglobulin heavy chain genes (VH-D-J). We characterized the frequency of SHM in expressed IgG mRNA immunoglobulin transcripts from control and HIV-1-infected patients. Design We compared utilization of genes in the most prominent VH family (VH3) and mutation frequencies and patterns of cDNA from VH3-IgG genes from 10 seronegative control subjects and 21 patients with HIV-1 infection (6 without and 15 patients with detectable plasma viremia). Methods Unique IgG VH3 family cDNA sequences (n = 1,565) were PCR amplified, cloned, and sequenced from blood. Sequences were analyzed using online (Vbase) and in-house immunoglobulin alignment resources. Results Mutation frequencies in the antigen-binding hypervariable complementarity determining regions (CDR1/2) of IgG class-switched B cells were lower among viremic HIV-1-infected patients vs. controls for nucleotides (CDR1/2: 10±5% vs. 13.5±6%, p = 0.03) and amino acids (CDR: 20%±10 vs. 25%±12, p = 0.02) and in structural framework regions. Mutation patterns were similar among groups. The most common VH3 gene, VH3-23, was utilized less frequently among viremic HIV-1-infected patients (p = 0.03), and overall, mutation frequencies were decreased in nearly all VH3 genes compared with controls. Conclusions B cells from HIV-1-infected patients show decreased mutation frequencies, especially in antigen-binding VH3 CDR genes, and selective defects in gene utilization. Similar mutation patterns suggest defects in the quantity, but not quality, of mutator activity. Lower levels of SHM in IgG class-switched B cells from HIV-1-infected patients may contribute to the increased risk of opportunistic infections and impaired humoral responses to preventative vaccines.

HIV INFECTION IN HEALTHCARE WORKERS

PreviewHealthcare workers know that there is a risk of HIV infection through exposure to AIDS patients. In both hospital and office settings, physicians have the opportunity to set standards and promote education about the degree of risk, effective precautions, and postexposure testing, prophylaxis, and treatment. Drs Henry and Thurn share the latest findings and offer policy recommendations based on their own experience.

Needlestick Injuries and Needle Disposal in Minnesota Nursing Homes

We examined needle use and disposal, needlestick injuries and their management, and employee education regarding the acquired immunodeficiency syndrome and needle use by means of a questionnaire sent to all long‐term care facilities certified for skilled care in Minnesota. Responses were received from 297 of 349 (85.1%) homes. Nearly all homes (271 of 293; 92.5%) provided education for new nursing employees about use and disposal of needles. Disposal of needles and sharps was generally consistent with current recommendations for short‐term care hospitals. Needlestick injuries were usually related to recapping and were most common in registered and licensed practical nurses but were infrequent (i.e., <1 injury per home per employee‐year) probably because parenteral therapy is infrequently used in long‐term care settings. Only slightly over half (166 of 286; 58%) of the homes had protocols for management of needlestick injuries.

Pseudomembranous colitis after itraconazole therapy

A 53-yr-old man was admitted with new onset of abdominal pain and nonbloody diarrhea 1 month after exposure to the antifungal agent itraconazole. Flexible sigmoidoscopy demonstrated the presence of pseudomembranes, and subsequent evaluation excluded other causes of diarrhea. Disruption of the resident fungal flora of the colon by itraconazole is proposed as the mechanism by which this patient developed pseudomembranous colitis. This association has not previously been reported.