Robert Belknap

University of Colorado Hospital, Denver, Colorado, United States

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Publications (16)53.24 Total impact

  • Robert Belknap, Charles L. Daley
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    ABSTRACT: Diagnosis of latent tuberculosis infection (LTBI) should be targeted toward individuals and groups with high risk of progression to active tuberculosis (TB). Low-risk populations should not be screened. Interferon-gamma release assays (IGRAs) perform as well or better than the tuberculin skin test in most targeted populations. IGRAs are preferred for bacille Calmette-Guérin (BCG)-vaccinated populations. A positive IGRA in a person at low risk for TB exposure should be confirmed with a repeat test or another method before recommending LTBI treatment. The choice of which IGRA to use is generally based on the costs and feasibility of performing the test.
    Clinics in Laboratory Medicine. 01/2014;
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    ABSTRACT: Rationale: Interferon gamma release assays (IGRAs) are alternatives to tuberculin skin testing (TST) for diagnosis of latent tuberculosis infection. Limited data suggest IGRAs may not perform well for serially testing healthcare workers (HCWs). Objective:Determine performance characteristics ofIGRAs vs. TST for serially testing HCWs. Methods:A longitudinal study involving 2563 HCWs undergoing occupationaltuberculosis screening at four healthcare institutions in the United States where the average tuberculosis case rate ranged from 4 to 9/100,000 persons.QuantiFERON®-TB Gold in-Tube (QFT-GIT), T-SPOT®.TB (T-SPOT), and TST were performed at baseline and every 6 months for 18 months between February 2008 and March 2011. Measurements and Main Results: 2418 HCWs completed baseline testing, which was positive for 125 (5.2%) by TST, 118 (4.9%) by QFT-GIT, and 144 (6.0%) by T-SPOT. A baseline positive TST with negative IGRAs was associated with Bacille Calmette- Guérin (BCG) vaccination (OR 25.1 [95% CI15.5, 40.5] vs. no BCG).Proportions of participants with test conversion during the study period were 138/2263 (6.1%) for QFTGIT, 177/2137 (8.3%) for T-SPOT, and 21/2293 (0.9%) for TST (p<0.001 for QFT-GIT vs. TST and for T-SPOT vs. TST; p=0.005 for QFT-GIT vs. T-SPOT). 81/106 (76.4%) QFT-GIT and 91/118 (77.1%) T-SPOT converters were negative when retested 6 months later. There was negative/positive discordance for 15/170 (8.8%) participants by QFTGIT and 19/151 (12.6%) by T-SPOT when blood was drawn two weeks later. Conclusions:Most conversions among HCWs in low TB incidence settings appear to be false-positives and these occurred 6-9 times more frequently with IGRAs than TST;repeat testing of apparent converters is warranted.
    American Journal of Respiratory and Critical Care Medicine 12/2013; · 11.04 Impact Factor
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    ABSTRACT: OBJECTIVE:: To develop preliminary data on Staphylococcus aureus (S. aureus) colonization and surgical site infections (SSI) in patients with open fractures who received standard antibiotic prophylaxis compared to a regimen including targeted MRSA coverage DESIGN:: randomized prospective clinical trial. PATIENTS:: adult patients who presented to the emergency department with an open fracture between April 2009 and July 2011. INTERVENTIONS:: 130 patients were randomized to receive prophylaxis with either cefazolin alone (control arm) or vancomycin and cefazolin (experimental arm) from presentation to the emergency department until 24 hours after the surgical intervention. Screening for S. aureus carriage was performed with nares swabs, predebridement and postdebridement open fracture wound swabs. Patients underwent prospective assessment for the development of SSI for no less than 30 days and up to 12 months. RESULTS:: Nasal colonization of methicillin sensitive S. aureus and MRSA among the sample were 20% and 3%, respectively. No significant difference in the rates of SSI was observed between the study arms (15% vs. 19%, respectively, p=0.62). S. aureus caused 55% of the deep incisional/organ space SSI, with 18% attributed to MRSA. A significantly higher rate of MRSA SSIs was observed among MRSA carriers compared with noncarriers (33% vs. 1%, respectively, p=0.003). CONCLUSIONS:: S. aureus nasal colonization in trauma patients with open fractures is similar to that of the general community. In this pilot study, the addition of vancomycin to standard antibiotic prophylaxis was found safe, but its efficacy should be evaluated in a larger multi-institutional trial. LEVEL OF EVIDENCE:: Therapeutic Level II. See Instructions for Authors for a complete26 description of levels of evidence.
    Journal of orthopaedic trauma 02/2013; · 1.78 Impact Factor
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    ABSTRACT: Poor adherence to tuberculosis (TB) treatment hinders the individual's recovery and threatens public health. Currently, directly observed therapy (DOT) is the standard of care; however, high sustaining costs limit its availability, creating a need for more practical adherence confirmation methods. Techniques such as video monitoring and devices to time-register the opening of pill bottles are unable to confirm actual medication ingestions. A novel approach developed by Proteus Digital Health, Inc. consists of an ingestible sensor and an on-body wearable sensor; together, they electronically confirm unique ingestions and record the date/time of the ingestion. A feasibility study using an early prototype was conducted in active TB patients to determine the system's accuracy and safety in confirming co-ingestion of TB medications with sensors. Thirty patients completed 10 DOT visits and 1,080 co-ingestion events; the system showed 95 . 0% (95% CI 93 . 5–96 . 2%) positive detection accuracy, defined as the number of detected sensors divided by the number of transmission capable sensors administered. The specificity was 99 . 7% [95% CI 99 . 2–99 . 9%] based on three false signals recorded by receivers. The system's identification accuracy, defined as the number of correctly identified ingestible sensors divided by the number of sensors detected, was 100%. Of 11 adverse events, four were deemed related or possibly related to the device; three mild skin rashes and one complaint of nausea. The system's positive detection accuracy was not affected by the subjects' Body Mass Index (p = 0 . 7309). Study results suggest the system is capable of correctly identifying ingestible sensors with high accuracy, poses a low risk to users, and may have high patient acceptance. The system has the potential to confirm medication specific treatment compliance on a dose-by-dose basis. When coupled with mobile technology, the system could allow wirelessly observed therapy (WOT) for monitoring TB treatment as a replacement for DOT. novel RaisinTM is currently under development that electronically confirms medication ingestions using an ingestible event marker (Proteus Digital Health, Inc. Redwood City, CA). There are no further patents, products in development, or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.
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    ABSTRACT: Poor adherence to tuberculosis (TB) treatment hinders the individual's recovery and threatens public health. Currently, directly observed therapy (DOT) is the standard of care; however, high sustaining costs limit its availability, creating a need for more practical adherence confirmation methods. Techniques such as video monitoring and devices to time-register the opening of pill bottles are unable to confirm actual medication ingestions. A novel approach developed by Proteus Digital Health, Inc. consists of an ingestible sensor and an on-body wearable sensor; together, they electronically confirm unique ingestions and record the date/time of the ingestion. A feasibility study using an early prototype was conducted in active TB patients to determine the system's accuracy and safety in confirming co-ingestion of TB medications with sensors. Thirty patients completed 10 DOT visits and 1,080 co-ingestion events; the system showed 95(.)0% (95% CI 93(.)5-96(.)2%) positive detection accuracy, defined as the number of detected sensors divided by the number of transmission capable sensors administered. The specificity was 99(.)7% [95% CI 99(.)2-99(.)9%] based on three false signals recorded by receivers. The system's identification accuracy, defined as the number of correctly identified ingestible sensors divided by the number of sensors detected, was 100%. Of 11 adverse events, four were deemed related or possibly related to the device; three mild skin rashes and one complaint of nausea. The system's positive detection accuracy was not affected by the subjects' Body Mass Index (p = 0(.)7309). Study results suggest the system is capable of correctly identifying ingestible sensors with high accuracy, poses a low risk to users, and may have high patient acceptance. The system has the potential to confirm medication specific treatment compliance on a dose-by-dose basis. When coupled with mobile technology, the system could allow wirelessly observed therapy (WOT) for monitoring TB treatment as a replacement for DOT.
    PLoS ONE 01/2013; 8(1):e53373. · 3.73 Impact Factor
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    ABSTRACT: Diabetic foot osteomyelitis is common and causes substantial morbidity, including major amputations, yet the optimal treatment approach is unclear. We evaluated an approach to limb salvage that combines early surgical debridement or limited amputation with antimicrobial therapy. We conducted a retrospective cohort study of patients treated between May 1, 2005, and May 31, 2007. The primary end point was cure, defined as not requiring further treatment for osteomyelitis of the affected limb. The secondary end point was limb salvage, defined as not requiring a below-the-knee amputation or a more proximal amputation. Fifty patients with diabetic foot osteomyelitis met the study criteria. Initial surgical management included local amputation in 43 patients (86%) and debridement without amputation in seven (14%). Most infections (n = 30; 60%) were polymicrobial, and Staphylococcus aureus was the most common pathogen (n = 23; 46%). Parenteral antibiotics were used in 45 patients (90%). Patients who had pathologic evidence of osteomyelitis at the surgical margin received therapy for a median of 43 days (interquartile range [IQR], 36-56 days), whereas those without evidence of residual osteomyelitis received therapy for a median of 19 days (IQR, 13-40 days). Overall, 32 patients (64%) were considered cured after a median follow-up of 26 months (IQR, 12-38 months). Fifteen of 18 patients (83%) who failed initial therapy were treated again with limb-sparing surgery. Limb salvage was achieved in 47 patients (94%), with only three patients (6%) requiring below-the-knee amputation. In patients with diabetic foot osteomyelitis, surgical debridement or limited amputation plus antimicrobial therapy is effective at achieving clinical cure and limb salvage.
    Journal of the American Podiatric Medical Association 07/2012; 102(4):273-7. · 0.77 Impact Factor
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    ABSTRACT: Multidrug (MDR)- and extensively drug-resistant (XDR) tuberculosis (TB) impose a heavy toll of human suffering and social costs. Controlling drug-resistant TB is a complex global public health challenge. Basic science advances including elucidation of the genetic basis of resistance have enabled development of new assays that are transforming the diagnosis of MDR-TB. Molecular epidemiological approaches have provided new insights into the natural history of TB with important implications for drug resistance. In the future, progress in understanding Mycobacterium tuberculosis strain-specific human immune responses, integration of systems biology approaches with traditional epidemiology and insight into the biology of mycobacterial persistence have potential to be translated into new tools for diagnosis and treatment of MDR- and XDR-TB. We review recent basic sciences developments that have contributed or may contribute to improved public health response.
    Respirology 03/2012; 17(5):772-91. · 2.78 Impact Factor
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    ABSTRACT: The QuantiFERON-TB Gold In-Tube assay (QFT) is increasingly being used for latent tuberculosis screening in patients infected with human immunodeficiency virus (HIV) in the United States. This is a retrospective analysis of repeating positive QFT assays as a strategy to identify false-positive results in HIV-infected patients at low risk for tuberculosis.
    Clinical Infectious Diseases 11/2011; 54(3):e20-3. · 9.37 Impact Factor
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    ABSTRACT: Infection is a feared complication and a common cause of loss of function following open fractures. Despite the evidence supporting the administration of prophylactic antibiotics after open fractures, data demonstrating the optimal regimen is lacking. We reviewed the data supporting the current prophylaxis recommendations and the changing epidemiology of Staphylococcus aureus, the most common cause of surgical site infection in patients with open fractures. Although widespread emergence of methicillin-resistant Staphylococcus aureus (MRSA) has been described in both hospital and community settings, to date, no studies have addressed the need for prophylaxis against MRSA in patients with open fractures. Until well-designed randomized trials are conducted, we recommend that providers consider selecting antibiotics active against MRSA for open fracture prophylaxis based on the local prevalence of MRSA carriage and individualized risk factors.
    Orthopedics 08/2011; 34(8):611-6; quiz 617. · 1.05 Impact Factor
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    ABSTRACT: Streptomycin has been available for over 60 years, yet optimal dosing in hemodialysis (HD) patients is not well defined. We report the successful treatment of enterococcal bacteremia in an HD patient with intravenous (IV) penicillin G and IV streptomycin at a dose of 7.5 mg/kg after HD sessions.
    Journal of Infection and Chemotherapy 02/2011; 17(5):698-9. · 1.55 Impact Factor
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    ABSTRACT: A simple serodiagnostic test based on the Mycobacterium leprae-specific phenolic glycolipid I(PGL-I), for individuals with leprosy is nearly universally positive in leprosy patients with high bacillary loads but cannot be used as a stand-alone diagnostic test for the entire spectrum of the disease process. For patients with early infection with no detectable acid-fast bacilli in lesions or with low or no antibody titer to PGL-I, as in those at the tuberculoid end of the disease spectrum, this diagnostic approach has limited usefulness. To identify additional M. leprae antigens that might enhance the serological detection of these individuals, we have examined the reactivity patterns of patient sera to PGL-I, lipoarabinomannan (LAM), and six recombinant M. leprae proteins (ML1877, ML0841, ML2028, ML2038, ML0380, and ML0050) by Western blot analysis and enzyme-linked immunosorbent assay (ELISA). Overall, the responses to ML2028 (Ag85B) and ML2038 (bacterioferritin) were consistently high in both multibacillary and paucibacillary groups and weak or absent in endemic controls, while responses to other antigens showed considerable variability, from strongly positive to completely negative. This analysis has given a clearer understanding of some of the differences in the antibody responses between individuals at opposite ends of the disease spectrum, as well as illustrating the heterogeneity of antibody responses toward protein, carbohydrate, and glycolipid antigens within a clinical group. Correlating these response patterns with a particular disease state could allow for a more critical assessment of the form of disease within the leprosy spectrum and could lead to better patient management.
    Clinical and vaccine Immunology: CVI 02/2011; 18(2):260-7. · 2.60 Impact Factor
  • M Kestler, R Reves, R Belknap
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    ABSTRACT: Post-operative reactivation of Mycobacterium tuberculosis (TB) is a recognized complication of surgery. We report a case of reactivation TB involving pacemaker wires and review the literature on surgical site TB infections following cardiac surgery to examine the clinical features and outcomes of this rare but important presentation of TB.
    The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 03/2009; 13(2):272-4. · 2.61 Impact Factor
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    ABSTRACT: Multidrug-resistant Acinetobacter baumannii has become a significant cause of healthcare-associated infections, but few reports have addressed Acinetobacter baumannii infections associated with orthopedic devices. The current recommended treatment for complicated infections due to orthopedic devices, including resistant gram-negative rods, consists of antimicrobial therapy with debridement and removal of implants. The patient, a 47-year-old woman, had previously had a prior total hip arthroplasty at 16 years of age for a complex femoral neck fracture, and multiple subsequent revisions. This time, she underwent a fifth revision secondary to pain. Surgery was complicated by hypotension resulting in transfer to the intensive care unit and prolonged respiratory failure. She received peri-operative cefazolin but postoperatively developed surgical wound drainage requiring debridement of a hematoma. Cultures of this grew ampicillin-sensitive Enterococcus and Acinetobacter baumannii (sensitive only to amikacin and imipenem). The patient was started on imipenem. Removal of the total hip arthroplasty was not recommended because of the recent surgical complications, and the patient was eventually discharged home. She was seen weekly for laboratory tests and examinations and, after 4 months of therapy, the imipenem was discontinued. She did well clinically for 7 months before recurrent pain led to removal of the total hip arthroplasty. Intra-operative cultures grew ampicillin-sensitive Enterococcus and coagulase-negative Staphylococcus but no multidrug-resistant Acinetobacter baumannii. The patient received ampicillin for 8 weeks and had not had recurrent infection at the time of writing, 37 months after discontinuing imipenem. We describe the successful treatment of an acute infection from multidrug-resistant Acinetobacter baumannii with debridement and retention of the total hip arthroplasty, using monotherapy with imipenem. This case challenges the general assumption that all orthopedic-device infections due to multidrug-resistant gram-negative organisms will require hardware removal. Further studies are needed to determine if organisms such as multidrug-resistant Acinetobacter baumannii are amenable to treatment with hardware retention.
    Journal of Medical Case Reports 03/2009; 3:45.
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    Robert Belknap, Kirsten Wall, Randall Reves
    American Journal of Respiratory and Critical Care Medicine 11/2008; 178(8):883-4; author reply 884. · 11.04 Impact Factor
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    ABSTRACT: Clostridium novyi has been associated with a large outbreak of severe infections in injection drug users. A case of bacteraemia with Clostridium butyricum in an injection drug user is reported. During treatment for Staphylococcus aureus osteomyelitis, the patient used an indwelling central venous catheter to inject cocaine. He was admitted with C. butyricum sepsis that responded to broad spectrum antibiotics, including vancomycin. Local investigation for other cases was unrevealing; however, growth of an unusual pathogen in clinical specimens should be investigated as it may represent a sentinel event with public health implications.
    Journal of Medical Microbiology 03/2008; 57(Pt 2):236-9. · 2.30 Impact Factor
  • Robert Belknap, Randall Reves, William Burman
    The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 10/2005; 9(9):1057-8. · 2.61 Impact Factor