Incidence, risk factors and distribution of syphilis in the end-stage renal disease population in the USA.

BACKGROUND: Syphilis is a sexually transmitted infection with an incidence of 14.9 cases per 100 000 persons in the USA in 2011. Untreated syphilis may remain quiescent for years but can also result in clinical sequelae, including neurosyphilis. End-stage renal disease (ESRD) patients may be at risk for syphilis due to a higher incidence of risk factors for the disease, including human immunodeficiency virus (HIV). Despite the presence of these risk factors, the incidence of syphilis in the ESRD population has not been reported. To address this issue, we investigated the incidence and risk factors for syphilis in the ESRD population using the United States Renal Data System (USRDS). METHODS: This study analyzed incident ESRD patients from 2004 to 2010. Based on International Classification of Diseases, Ninth Revision codes for syphilis, we determined the incidence and risk factors for syphilis following an inpatient diagnosis. Generalized linear modeling was used to examine the relative risk (RR) for the disease when controlling for demographic and other clinical risk factors. RESULTS: A total of 383 diagnoses of syphilis were identified after screening 759 066 patients. The 8-year incidence of any type of syphilis was 50.45 cases per 100 000 person-years. Other unspecified syphilis (29.77 cases per 100 000 person-years) and neurosyphilis (10.93 cases per 100 000 person-years) were the most common diagnoses. The greatest incidence was found on the East and West Coasts. Patients with the disease were younger and more likely to be black and non-Hispanic. In the final model, the adjusted RR for syphilis was significantly increased with HIV (7.61), hepatitis C (3.57), herpes simplex (2.06) and hepatitis B (1.75). CONCLUSIONS: The incidence of syphilis is >3-fold greater in ESRD patients when compared with the general population and is associated with sexually transmitted viral infections. Neurosyphilis is a common occurrence and is treatable, suggesting that all assessments of confusion in dialysis patients should include screening for the disease.

Severe and Progressive Cellulitis Caused by Serratia marcescens Following a Dog Scratch.

Soft tissue infections occur in over 30% of patients with chemotherapy-induced neutropenia. Gram-positive bacterial infections predominate early in neutropenia, and likelihood of infection by resistant bacteria and fungi increases with prolonged neutropenia. Prior infections and exposures influence the risk of rare pathogens. A 55-year-old woman with chemotherapy-induced neutropenia was scratched on her forearm by a dog. She cleaned the wound with isopropanol and was treated empirically with amoxicillin-clavulanate. Over the next 4 days, she developed fever along with erythema, edema, and mild tenderness of the forearm without purulence or crepitus. She was hospitalized and received empiric treatment with intravenous vancomycin, piperacillin-tazobactam, tobramycin, and voriconazole. Despite therapy, her fevers persisted and the cellulitis progressed for over a week. After 10 days of hospitalization, her neutrophil count began to recover and a bulla developed at the wound site. Culture of the bullous fluid grew Serratia marcescens, and antibiotics were switched to cefepime based on susceptibility. She defervesced and showed substantial improvement of cellulitis within 48 hours and was discharged on oral ciprofloxacin. Serratia marcescens skin infections are rare, and this may be the first report of Serratia cellulitis associated with trauma from dog contact. This case highlights the need to consider unusual pathogens based on exposure history and immune status and to obtain cultures from fluid collections or tissue in cases of treatment-resistant soft tissue infections.

An Iterative, Synthetic Approach To Engineer a High-Performance PhoB-Specific Reporter.

Transcriptional reporters are common tools for analyzing either the transcription of a gene of interest or the activity of a specific transcriptional regulator. Unfortunately, the latter application has the shortcoming that native promoters did not evolve as optimal readouts for the activity of a particular regulator. We sought to synthesize an optimized transcriptional reporter for assessing PhoB activity, aiming for maximal "on" expression when PhoB is active, minimal background in the "off" state, and no control elements for other regulators. We designed specific sequences for promoter elements with appropriately spaced PhoB-binding sites, and at 19 additional intervening nucleotide positions for which we did not predict sequence-specific effects, the bases were randomized. Eighty-three such constructs were screened in Vibrio fischeri, enabling us to identify bases at particular randomized positions that significantly correlated with high-level "on" or low-level "off" expression. A second round of promoter design rationally constrained 13 additional positions, leading to a reporter with high-level PhoB-dependent expression, essentially no background, and no other known regulatory elements. As expressed reporters, we used both stable and destabilized variants of green fluorescent protein (GFP), the latter of which has a half-life of 81 min in V. fischeri In culture, PhoB induced the reporter when phosphate was depleted to a concentration below 10 µM. During symbiotic colonization of its host squid, Euprymna scolopes, the reporter indicated heterogeneous phosphate availability in different light-organ microenvironments. Finally, testing this construct in other members of the Proteobacteria demonstrated its broader utility. The results illustrate how a limited ability to predict synthetic promoter-reporter performance can be overcome through iterative screening and reengineering.IMPORTANCE Transcriptional reporters can be powerful tools for assessing when a particular regulator is active; however, native promoters may not be ideal for this purpose. Optimal reporters should be specific to the regulator being examined and should maximize the difference between the "on" and "off" states; however, these properties are distinct from the selective pressures driving the evolution of natural promoters. Synthetic promoters offer a promising alternative, but our understanding often does not enable fully predictive promoter design, and the large number of alternative sequence possibilities can be intractable. In a synthetic promoter region with over 34 billion sequence variants, we identified bases correlated with favorable performance by screening only 83 candidates, allowing us to rationally constrain our design. We thereby generated an optimized reporter that is induced by PhoB and used it to explore the low-phosphate response of V. fischeri This promoter design strategy will facilitate the engineering of other regulator-specific reporters.