Erik Munson

Epidemiology and Outcome of Nosocomial and Community-Onset Bloodstream Infection

ABSTRACT We performed a prospective study of bloodstream infection to determine factors independently associated with mortality. Between February 1999 and July 2000, 929 consecutive episodes of bloodstream infection at two tertiary care centers were studied. An ICD-9-based Charlson Index was used to adjust for underlying illness. Crude mortality was 24% (14% for community-onset versus 34% for nosocomial bloodstream infections). Mortality attributed to the bloodstream infection was 17% overall (10% for community-onset versus 23% for nosocomial bloodstream infections). Multivariate logistic regression revealed the independent associations with in-hospital mortality to be as follows: nosocomial acquisition (odds ratio [OR] 2.6, P < 0.0001), hypotension (OR 2.6, P < 0.0001), absence of a febrile response (P = 0.003), tachypnea (OR 1.9, P = 0.001), leukopenia or leukocytosis (total white blood cell count of <4,500 or >20,000, P = 0.003), presence of a central venous catheter (OR 2.0, P = 0.0002), and presence of anaerobic organism (OR 2.5, P = 0.04). Even after adjustments were made for underlying illness and length of stay, nosocomial status of bloodstream infection was strongly associated with increased total hospital charges (P < 0.0001). Although accounting for about half of all bloodstream infections, nosocomial bloodstream infections account for most of the mortality and costs associated with bloodstream infection.

Detection and Treatment of Bloodstream Infection: Laboratory Reporting and Antimicrobial Management

ABSTRACT We analyzed antimicrobial use in 509 episodes of clinically significant bloodstream infection to assess the impact that microbiology laboratory reporting had on antimicrobial management. Most therapy interventions occurred at the time of phlebotomy and after notification of Gram stain results by telephone. Release of antimicrobial susceptibility data had the least impact on antimicrobial management.

Occurrence of Severe Destructive Lyme Arthritis in Hamsters Vaccinated with Outer Surface Protein A and Challenged with Borrelia burgdorferi

ABSTRACT Arthritis is a frequent and major complication of infection withBorrelia burgdorferi sensu stricto. The antigens responsible for the induction of arthritis are unknown. Here we provide direct evidence that a major surface protein, outer surface protein A (OspA), can induce arthritis. Hamsters were vaccinated with 30, 60, or 120 μg of recombinant OspA (rOspA) in aluminum hydroxide and challenged with B. burgdorferi sensu stricto isolate 297 or C-1-11. Swelling of the hind paws was detected in 100, 100, and 50% of hamsters vaccinated with 30, 60, or 120 μg of rOspA, respectively. In addition, arthritis developed in 57% of hamsters vaccinated with a canine rOspA vaccine after infection with B. burgdorferisensu stricto. When the canine rOspA vaccine was combined with aluminum hydroxide, all vaccinated hamsters developed arthritis after challenge with B. burgdorferi sensu stricto. Histopathologic examination confirmed the development of severe destructive arthritis in rOspA-vaccinated hamsters challenged with B. burgdorferisensu stricto. These findings suggest that rOspA vaccines should be modified to eliminate epitopes of OspA responsible for the induction of arthritis. Our results are important because an rOspA vaccine in aluminum hydroxide was approved by the Food and Drug Administration for use in humans.

Impact of Trichomonas vaginalis Transcription-Mediated Amplification-Based Analyte-Specific-Reagent Testing in a Metropolitan Setting of High Sexually Transmitted Disease Prevalence

ABSTRACT Trichomoniasis is a significant sexually transmitted disease (STD) in the spectrum of public health and primary care because of its association with agents such as human immunodeficiency virus and Neisseria gonorrhoeae. However, its true significance may be underestimated due to diagnostic modalities that exhibit poor sensitivity. A total of 1,086 genital specimens from two urban emergency departments, a suburban urgent-care facility, and a metropolitan outpatient physician group were subjected to transcription-mediated amplification-based Trichomonas vaginalis analyte-specific-reagent (ASR) testing (Gen-Probe, Inc.). The rate of positive molecular ASR results (14.5%) doubled that of direct saline preparation (7.0%; P < 0.0002). Analogous increases were observed at one emergency department and within the outpatient physician group (P < 0.0002). No significant increase in the rate of positive molecular ASR results was observed from the facilities that encountered a lower frequency of black/African American patients. While positive T. vaginalis findings via direct saline preparation did not have a significant association with concomitant Chlamydia trachomatis or N. gonorrhoeae infection overall, a positive T. vaginalis ASR result was a better predictor of concomitant C. trachomatis or N. gonorrhoeae infection (odds ratios of 2.34 and 4.46, respectively; P < 0.0001). The increased rate of positive T. vaginalis ASR results was observed in both point-of-care (P = 0.02 versus direct saline preparation) and laboratory (P = 0.003) testing. Highly sensitive T. vaginalis molecular ASR not only transcends issues of specimen integrity and microscopic acumen but also has an increased ability to predict the likelihood of additional STDs in defined populations.

Destructive Arthritis in Vaccinated Interferon Gamma-Deficient Mice Challenged with Borrelia burgdorferi: Modulation by Tumor Necrosis Factor Alpha

ABSTRACT We found that Borrelia burgdorferi-vaccinated gamma interferon-deficient (IFN-γ0) mice challenged with B. burgdorferi developed prominent chronic destructive osteoarthropathy. When these mice were treated with anti-tumor necrosis factor alpha (TNF-α) antibody, the severity of the destructive osteoarthritis was enhanced and affected the mobility of the animals. In addition, extensive swelling of the hind paws occurred. In contrast, treatment of B. burgdorferi-vaccinated, challenged IFN-γ0 mice with recombinant TNF-α (rTNF-α) inhibited the development of arthritis, including swelling of the hind paws. Moreover, treatment of vaccinated, challenged IFN-γ0 mice with anti-TNF-α inhibited fourfold the production of an antibody that kills B. burgdorferi, while treatment of vaccinated, challenged IFN-γ0 mice with rTNF-α slightly elevated the level of the borreliacidal antibody. These results suggest that the level of TNF-α directly or indirectly regulates the production of borreliacidal antibody and the development of vaccine-induced destructive Lyme osteoarthritis. Studies are in progress to determine the mechanism by which TNF-α-dependent cytokines generate the destructive arthritis.

Comparison of Carrot Broth- and Selective Todd-Hewitt Broth-Enhanced PCR Protocols for Real-Time Detection of Streptococcus agalactiae in Prenatal Vaginal/Anorectal Specimens

ABSTRACT The reporting of accurate Streptococcus agalactiae screening results in a short time frame is of tremendous clinical benefit. A total of 203 consecutive primary vaginal/anorectal specimens were cultured in selective Todd-Hewitt broth (LIM broth) and with the StrepB carrot broth kit (carrot broth). One-day broth cultures were subjected to both centrifugation and clarification of a 500-μl aliquot prior to sample lysis (protocol A) and direct lysis of a 50-μl aliquot (protocol B). The lysates were subsequently analyzed by the BD GeneOhm StrepB assay. The results were compared to the carrot broth culture results derived from visualization of pigment on day 1 or from a subculture of carrot broth. Thirty-four carrot broth cultures (16.7%) generated diagnostic pigment following overnight incubation; an additional 26 (12.8%) were positive for S. agalactiae upon subculture. Carrot broth-enhanced PCR by the use of either protocol A or protocol B trended toward a higher rate of positive results (33.0%) than the rate observed by either the LIM broth-enhanced PCR (30.5%) or full carrot broth culture analysis (29.6%). In the context of the result on day 1, both carrot broth- and LIM broth-enhanced PCRs generated more true-positive results (P < 0.001) than carrot broth culture visualization. The predictive values for both protocols of carrot broth- or LIM broth-enhanced PCR were ≥95.4%. Whereas protocol A resolved the results for 99.8% of the specimens in the evaluation upon initial testing, a 5.7% initial unresolved rate and a 1.5% final unresolved rate were determined by the use of protocol B. The use of carrot broth within a rapid and highly accurate molecular reflex testing algorithm can limit follow-up testing to cultures without evidence of pigmentation.

Screening of Male Patients for Trichomonas vaginalis with Transcription-Mediated Amplification in a Community with a High Prevalence of Sexually Transmitted Infection

ABSTRACT Trichomonas vaginalis infection in males has been largely uncharacterized. Past reports indicated increased susceptibility to other sexually transmitted infection (STI) agents such as human immunodeficiency virus and Neisseria gonorrhoeae with concurrent T. vaginalis infection. This warrants a more thorough review of male T. vaginalis incidence. A retrospective 3-year investigation of transcription-mediated amplification (TMA)-based urethral swab and first-void urine screening for T. vaginalis within a regional health care system was performed to address T. vaginalis prevalence in males. Of 622 total samples tested, 6.6% were positive for T. vaginalis. Delineation of all specimens by ZIP code of patient residence revealed 11 predominant ZIP codes with respect to testing volume and detection rates. Within these 11 ZIP codes, representing 78.3% of total testing volume, urine was the preferred specimen source compared to urethral swabs. Seven of these 11 ZIP codes contained majority African American populations. The aggregate T. vaginalis detection rate trended higher than that of the remaining four ZIP codes, which were comprised primarily of Caucasian populations (8.9% versus 5.0%, respectively; P = 0.15). The average age of a T. vaginalis-infected male (39.9 years) was significantly greater than those for Chlamydia trachomatis or N. gonorrhoeae (27.6 and 25.9 years, respectively; P < 0.001). Given the significant rate of T. vaginalis detection, with age distribution analogous to that reported in females, TMA-based detection of T. vaginalis can be a routine constituent within a comprehensive STI screening panel for males in high-prevalence STI communities.

Female Epidemiology of Transcription-Mediated Amplification-Based Trichomonas vaginalis Detection in a Metropolitan Setting with a High Prevalence of Sexually Transmitted Infection

ABSTRACT Recent literature has reported increased accuracy of Trichomonas vaginalis transcription-mediated amplification (TMA)-based analyte-specific reagent (ASR) testing in female populations. A retrospective investigation assessed 7,277 female first-void urine, cervical, or vaginal specimens submitted from a high-prevalence sexually transmitted infection (STI) community to characterize prevalence of disease etiologies. The most common STI phenotype reflected detection of solely T. vaginalis (54.2% of all health care encounters that resulted in STI detection). In females with detectable T. vaginalis, codetection of Chlamydia trachomatis and Neisseria gonorrhoeae occurred in 7.8% and 2.7% of health care encounters, respectively. The mean age of women with detectable T. vaginalis (30.6) was significantly higher than those for women with C. trachomatis or N. gonorrhoeae (22.3 and 21.6, respectively; P < 0.0001). T. vaginalis was the predominant sexually transmitted agent in women over the age of 20 (P < 0.0002). C. trachomatis was the most commonly detected agent in females under the age of 21, particularly from cervical specimens. However, first-void urine detection rates for T. vaginalis and C. trachomatis within this age demographic demonstrated no difference (P = 0.92). While overall and cervical specimen-derived detection of T. vaginalis within African American majority geographical locales outweighed that within majority Caucasian geographical regions (P ≤ 0.004), this difference was not noted with first-void urine screening (P = 0.54). Health care professionals can consider TMA-based T. vaginalis screening for a wide age range of patients; incorporation of first-void urine specimens into screening algorithms can potentiate novel insight into the epidemiology of trichomoniasis.

Modification of dienes mutual inhibition test for epidemiological characterization of Pseudomonas aeruginosa isolates.

ABSTRACT Pseudomonas aeruginosa is an important cause of community-associated and nosocomial infections related to exposure to aqueous environments. Such infections often occur in the setting of a common-source outbreak, in which case epidemiological characterization of isolates may be necessary. In this preliminary study, a modification of the Dienes mutual inhibition test, ordinarily used to assess the relatedness of swarming Proteus mirabilis strains, was used to study 15 P. aeruginosa isolates, with the results compared to those obtained by ribotype analysis. Complete concordance was noted between the results of the Dienes test and those of ribotyping. These observations suggest that further studies are warranted to assess the utility of the modified Dienes test as a simple, inexpensive, and reliable means for epidemiological typing of P. aeruginosa.

Macrophages interact with enriched populations of distinct T lymphocyte subsets for the induction of severe destructive Lyme arthritis.

Severe destructive Lyme arthritis was detected in the hind paws of hamsters infused with enriched populations of either CD4+ or CD4‐ T lymphocytes along with macrophages exposed in vitro to formalin‐inactivated Borrelia burgdorferi and then infected with the Lyme spirochete. Swelling was detected 4 days after infection, increased rapidly, peaked on day 8 of infection, and gradually decreased. Similarly, severe destructive arthritis was induced in hamsters infused with enriched populations of unfractionated T lymphocytes and macrophages exposed to spirochetes after infection with B. burgdorferi. Histopathological examination affirmed that hamsters infused with CD4+, CD4‐, or unfractionated T lymphocytes and macrophages exposed to B. burgdorferi‐induced arthritis. In addition, macrophages exposed in vitro to B. burgdorferi demonstrated both conventional and coiling phagocytosis, suggesting a mechanism by which CD4+ and CD4‐ T lymphocytes induce arthritis, respectively. These findings demonstrate that both CD4+ and CD4‐ subpopulations of T lymphocytes are capable of interacting with macrophages for the induction of severe destructive Lyme arthritis. J. Leukoc. Biol. 65: 162–170; 1999.