Sam approaching a scent detection box, where she correctly identified a UTI sample. Good girl! (Maurer 2016)
Sit. Stay. Roll over. Diagnose an infection? It seems that, in addition to being man’s best friend, dogs make pretty good infectious disease doctors. Or at least that’s the conclusion of two studies which trained dogs to identify UTIs or C. difficile infections in real patient samples. The results were impressive!
In the first study, Sam (pictured right) and other dogs were trained to identify the presence of bacteria. They were then tested with 687 urine samples, one-third of which were infected. These dogs correctly identified the UTI samples at near 100% accuracy. This stellar success rate was not affected by pathogen either, as dogs were able to identify E. coli, Enterococcus, Klebsiella, and S. aureus all at greater than 99% sensitivity and 91% specificity. Even when samples were diluted 1:1000, UTI samples were correctly identified 100% of the time.
Chase (Top), a Border Collie Pointer and Piper (Bottom), a German Shepherd who were trained to identify C. difficile in stool samples. (Taylor 2018)
In another study, two dogs (Piper and Chase, pictured left) were trained to identify toxin-positive C. difficile in stool samples, which they were able to do at 80-90% sensitivity and ~85% specificity.
While you are unlikely to start seeing dogs in your local microbiology laboratory any time soon, this phenomenon is not without real-world applications. As the first study notes in its discussion:
“One month after the study was completed, 1 of the dogs (Abe) spontaneously alerted to a person visiting the training center. The patient had been feeling ill, but had not suspected a UTI. Based on Abe’s alerting behavior, the patient had a medical exam and a urine culture was performed the next day, and physicians confirmed bacteriuria and a clinical diagnosis of UTI.”
That being said, there is a leap between the olfactory doggy detection of bacteria and the clinical diagnosis of infectious syndromes based on symptoms…and I can’t even get my dog to consistently lay down on command. For more details, methods, and study design, see the links below.
Study 1: Maurer M, McCulloch M, Willey AM, Hirsch W, Dewey D. Detection of Bacteriuria by Canine Olfaction. Open Forum Infect Dis. 2016;3(2):ofw051. Published 2016 Mar 9. doi:10.1093/ofid/ofw051
Study 2: Taylor MT, McCready J, Broukhanski G, Kirpalaney S, Lutz H, Powis J. Using Dog Scent Detection as a Point-of-Care Tool to Identify Toxigenic Clostridium difficile in Stool. Open Forum Infect Dis. 2018;5(8):ofy179. Published 2018 Aug 22. doi:10.1093/ofid/ofy179
Associate Professor, Department of Internal Medicine Associate Medical Director, Infection Control & Epidemiology Co-Director, Digital Innovation and Social Media Strategy
Dr. Cawcutt is an author on a new review article focusing on the relationship between infection and chronic pain persisting even after resolution of acute illness.
Acute infection can cause chronic pain?
Yes, it can. Pain is a common feature accompanying infection and one of the hallmark features of inflammation. While most infections are cleared by the body, with or without medical intervention, this pain can stick around long after the pathogen is gone.
How does this happen?
There are many different ways this can happen, many of which are explained in detail in this article. In general, the stress of an infection or the medical treatments of infection on the body can cause the immune system to continue to act long past pathogen eradication.
Where can I read more?
For a more technical (and interesting!) rationale for molecular mimicry, central nervous system sensitization, bystander activation, and antimicrobial toxicity in causing chronic post-infectious pain, see the linked article. You will also find additional information on the common bacterial, viral, psychogenic and pharmaceutical causes of post-infectious pain syndromes.
The Division of Infectious Diseases at the University of Nebraska Medical Center in Omaha, NE is recruiting an infectious diseases physician with interests or experience in infection prevention/healthcare epidemiology to serve as the Medical Director of the Infection Control Assessment and Promotion Program (ICAP). This is an exciting opportunity to lead, manage, and direct continued development of the ICAP. You will serve as an expert advisor to the NE Department of Health and Human Services and lead a multidisciplinary team of professionals including infection preventionists, infectious diseases physicians, and ID-trained pharmacists. The physician hired will have the opportunity for a gratifying faculty position and career in the UNMC Division of Infectious Diseases and will be expected to participate fully in the clinical, education, and research missions of the Division.
Pictured left, the Infection Control Assessment and Promotion Program (ICAP) and Nebraska Antimicrobial Stewardship Assessment and Promotion Program (ASAP) team.
About ICAP: Working closely with the Nebraska Department of Health and Human Services, ICAP offers no cost, peer-to-peer infection control assessments and recommendations. Our goal is to improve infection prevention practices in a broad range of healthcare settings and improve the capability to respond to infectious disease outbreaks. This model is unique in bringing experienced “outside eyes” to individual hospitals, long-term care centers, dialysis centers and outpatient/surgery centers.
Know the perfect person for this opportunity? Please spread the word and share this application.
Current Clinical Scholar Dan Ramirez, PharmD, and program coordinator Nikki Regan at a recent conference supported by the Clinical Scholars program.
The UNMC/Nebraska Medicine Specialty Care Center is looking for minority or predominantly minority-serving, front-line clinical care providers to participate in a 12 month HIV prevention, diagnosis and management mentorship program.
The Clinical Scholars Program is sponsored by the Midwest AIDS Education and Training Center. The program is open to clinical care providers including physicians, PAs, APRNs, and pharmacists, and provides a FREE one year training course consisting of didactic and preceptorship opportunities. Applicants should have a basic understanding of HIV, and be motivated to apply general principles of HIV prevention, management and care collaboration to their primary care or related practice.
Professor, Department of Internal Medicine Chief, Division of Infectious Diseases Medical Director, Infection Control & Epidemiology Associate Medical Director, Antimicrobial Stewardship
Dr. Rupp recently assisted in the creation of new clinical guidelines aimed at prevention of central line-associated bloodstream infections.
What are clinical guidelines and why are they important?
Clinical guidelines are a crucial component of evidence-based medicine. They are issued to standardize medical care across the nation and are often determined using an extensive literature review process with input from panels of experts in the field. These guidelines were updated with input from the Society for Healthcare Epidemiology of America (SHEA), the Infectious Diseases Society of America (IDSA), the Association for Professionals in Infection Control and Epidemiology (APIC), the American Hospital Association (AHA), and The Joint Commission, as well as representation by the Centers for Disease Control and Prevention (CDC).
Why do guidelines need to be updated?
Best medical practices are often a moving target, especially in infectious disease. Pathogens change over time, as does medical technology and the scientific literature describing clinical problems. Guideline updates are one of the most straightforward ways that research can update clinical practice to ensure we are always acting in the best interest of patients.
What are the major changes in this guideline update?
There are 4 major changes with this 2022 update:
The subclavian vein is recommended for central venous catheter (CVC) insertion in the intensive care setting. Previous recommendations advised avoiding femoral vein for access, which remains valid.
Ultrasound guidance for catheter insertion is bolstered by greater evidence and now is more strongly recommended, although strict attention to sterile technique is advised.
The use of chlorhexidine-containing dressings is now considered an “essential practice”; previously, this was recommended only during periods of high infectious risk.
Routine replacement of administration sets not used for blood, blood products, or lipid formulations can be performed at intervals of up to 7 days, instead of the previous recommended interval of no longer than 4 days.
Are there any other changes?
Yes! There are several other guideline changes outlined in the updated guidelines. For details, guideline creation methods, and additional changes, see the full guideline document here.
Thanks to Dr. Rupp for his contribution to this vital process to evidence-based medicine!
A #PharmToExamTable question about MRSA treatment, answered byTraver Pettijohn, PharmD, a 2021 Graduate of UNMC College of Pharmacy who is now a pharmacist at Community Pharmacy.
(Reviewed by Andrew Watkins, PharmD)
Pneumonia, S. aureus, and PVL
Pneumonia is an infection of the lungs caused by the infiltration of microorganisms, such as bacteria, viruses, and fungi, into the lungs of hosts. Many patients diagnosed with bacterial pneumonia are able to be treated in the outpatient setting with oral antibiotics; however, more serious cases may require hospitalization and more aggressive treatment. Staphylococcus aureus is a gram positive, pyogenic bacteria that is associated with superficial skin and soft tissue infections as well as deeper infections including septic arthritis, osteomyelitis, endocarditis, and pneumonia. Community acquired methicillin-resistant S. aureus (CA-MRSA) is of particular concern as it is resistant to beta-lactam antibiotics, which are first-line empiric therapy for many community acquired infections. CA-MRSA has been associated with a form of necrotizing pneumonia (NP) characterized by leukopenia, hemoptysis, and extensive destruction of lung tissue.
Panton-Valentine Leukocidin (PVL) is an exotoxin that is produced by many strains of S. aureus and attacks host immune cells. The majority of CA-MRSA strains in the US produce PVL, which increases the risk of developing necrotizing pneumonia.1 There is controversy surrounding the role PVL plays in CA-MRSA infections in general, but the most compelling data has shown the association of PVL with post-viral NP.2,3 Several studies evaluating PVL as a virulence factor for NP in mice have largely been inconclusive3-8. One study using a rabbit model has demonstrated that PVL plays a critical role in NP infection9. The authors of this study state PVL production is believed to result in the activation of polymorphonuclear (PMN) leukocytes and macrophages, along with accompanying inflammatory cytokines. Once these immune cells are recruited to the site of infection, PVL lyses PMNs, resulting in the release of granules and proteolytic enzymes into the lung tissue which leads to tissue damage.
There have been limited trials assessing the use of antimicrobials for the purpose of toxin suppression in PVL positive CAP, and their place in therapy of NP is thought to be analogous to their role in the treatment of streptococcal and staphylococcal toxic shock syndrome. All studies to date evaluating toxin suppression in PVL producing CA-MRSA strains have been in vitro studies with clindamycin and linezolid being the two most studied and most successful antibiotics for toxin suppression. Current IDSA/ATS Community Acquired Pneumonia (CAP) guidelines do not address the use of antimicrobials for toxin suppression in NP caused by CA-MRSA.10IDSA guidelines for treatment of MRSA infections do not recommend the routine use of clindamycin or linezolid in treating CA-MRSA except in severe cases of NP as there is limited evidence to support their use.11 The evidence supporting the anti-toxin effects of clindamycin and linezolid in CA-MRSA infections is summarized below.
Clindamycin, Linezolid, and Toxin Suppression
Clindamycin is a lincosamide antibiotic which works by binding the 50s ribosomal subunit of bacteria thus disrupting protein synthesis and creating a bacteriostatic effect. S. aureus bacteria can develop resistance to clindamycin by modification of the 23s ribosome target site that is either inducible or constitutive, with the latter preventing toxin suppression completely in vitro.13,14 Three in vitro studies performed using direct PVL toxin quantification showed that clindamycin inhibited the production of PVL toxin at sub inhibitory concentrations (concentrations below the MIC) as low as 1/8 MIC.12,14,15 Two in vitro studies quantified toxin suppression by measuring mRNA targets in culture media incubated with clindamycin concentrations as low as 1/8 MIC also showed significant reduction in PVL expression.16,17 One study utilized a hollow fiber in vitro model which is a two compartment pharmacokinetic/pharmacodynamics model that optimizes drug delivery and allows for simulation of sequestered infections. Clindamycin was then introduced to the model for incubation at a level that simulated the pharmacokinetics of the standard treatment dose of various antibiotics. This study then evaluated mRNA levels for gene expression of various toxins. Clindamycin at exposures simulating 600 mg every 8 hours demonstrated a significant downtrend in PVL toxin gene expression over 48 hours of incubation.16
Linezolid is an oxazolidinone antibiotic which inhibits bacterial growth by disrupting the initiation process of protein synthesis and creates a bacteriostatic effect. Linezolid is a much newer antibiotic compared to clindamycin, thus there is less evidence supporting its use in toxin suppression. The previously mentioned study utilizing a hollow fiber in vitro model found linezolid dosed at 600mg every 12 hours to be effective at suppressing PVL gene expression for up to 24 hours.16 Two studies showed a reduction in PVL gene expression with linezolid and another study showed a decrease in direct PVL toxin quantity.14,16,17 Another study evaluated PVL toxin levels with subinhibitory concentrations of linezolid found that linezolid induced a concentration-dependent decrease in PVL level starting at concentrations as low as 1/8 or 1/4 MIC.15
In Summary…
In vitro data supports the ability of both clindamycin and linezolid to suppress the production of PVL toxin in CA-MRSA isolates. The clinical utility of this information is still an area of future research. The association of PVL toxin with virulence of CA-MRSA has only been well established for necrotizing pneumonia and not for other types of PVL producing CA-MRSA infections. Clinical guidelines for MRSA treatment do not yet recommend the routine use of these antimicrobials for the purpose of toxin suppression. These antimicrobials carry their own risk of adverse events and should only be considered for use by experts in certain clinical scenarios. In vitro data also shows that subinhibitory concentrations of these drugs can inhibit toxin production; however, dosing regimens aimed to achieve these MICs in the site of infection in vivo have yet to be evaluated.
References
1. Chambers HF. Community-associated MRSA–resistance and virulence converge. N Engl J Med. 2005;352(14):1485-1487. doi:10.1056/NEJMe058023
2. Francis JS, Doherty MC, Lopatin U, et al. Severe community-onset pneumonia in healthy adults caused by methicillin-resistant Staphylococcus aureus carrying the Panton-Valentine leukocidin genes. Clin Infect Dis. 2005;40(1):100-107. doi:10.1086/427148
3. Hageman JC, Uyeki TM, Francis JS, et al. Severe community-acquired pneumonia due to Staphylococcus aureus, 2003-04 influenza season. Emerg Infect Dis. 2006;12(6):894-899. doi:10.3201/eid1206.051141
4. Brown EL, Dumitrescu O, Thomas D, et al. The Panton-Valentine leukocidin vaccine protects mice against lung and skin infections caused by Staphylococcus aureus USA300. Clin Microbiol Infect. 2009;15(2):156-164. doi:10.1111/j.1469-0691.2008.02648.x
5. Voyich JM, Otto M, Mathema B, et al. Is Panton-Valentine leukocidin the major virulence determinant in community-associated methicillin-resistant Staphylococcus aureus disease?. J Infect Dis. 2006;194(12):1761-1770. doi:10.1086/509506
6. Bubeck Wardenburg J, Bae T, Otto M, Deleo FR, Schneewind O. Poring over pores: alpha-hemolysin and Panton-Valentine leukocidin in Staphylococcus aureus pneumonia. Nat Med. 2007;13(12):1405-1406. doi:10.1038/nm1207-1405
7. Bubeck Wardenburg J, Palazzolo-Ballance AM, Otto M, Schneewind O, DeLeo FR. Panton-Valentine leukocidin is not a virulence determinant in murine models of community-associated methicillin-resistant Staphylococcus aureus disease. J Infect Dis. 2008;198(8):1166-1170. doi:10.1086/592053
8. Bubeck Wardenburg J, Palazzolo-Ballance AM, Otto M, Schneewind O, DeLeo FR. Panton-Valentine leukocidin is not a virulence determinant in murine models of community-associated methicillin-resistant Staphylococcus aureus disease. J Infect Dis. 2008;198(8):1166-1170. doi:10.1086/592053
9. Diep BA, Chan L, Tattevin P, et al. Polymorphonuclear leukocytes mediate Staphylococcus aureus Panton-Valentine leukocidin-induced lung inflammation and injury. Proc Natl Acad Sci U S A. 2010;107(12):5587-5592. doi:10.1073/pnas.0912403107
10. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019;200(7):e45-e67. doi:10.1164/rccm.201908-1581ST
11. Liu C, Bayer A, Cosgrove SE, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections in Adults and Children, Clinical Infectious Diseases, Volume 52, Issue 3, 1 February 2011, Pages e18–e55, https://doi.org/10.1093/cid/ciq146
12. Hodille E, Badiou C, Bouveyron C, et al. Clindamycin suppresses virulence expression in inducible clindamycin-resistant Staphylococcus aureus strains. Ann Clin Microbiol Antimicrob. 2018;17(1):38. Published 2018 Oct 20. doi:10.1186/s12941-018-0291-8
13. Herbert S, Barry P, Novick RP. Subinhibitory clindamycin differentially inhibits transcription of exoprotein genes in Staphylococcus aureus. Infect Immun. 2001;69(5):2996-3003. doi:10.1128/IAI.69.5.2996-3003.2001
14. Stevens DL, Ma Y, Salmi DB, McIndoo E, Wallace RJ, Bryant AE. Impact of antibiotics on expression of virulence-associated exotoxin genes in methicillin-sensitive and methicillin-resistant Staphylococcus aureus. J Infect Dis. 2007;195(2):202-211. doi:10.1086/510396
15. Dumitrescu O, Boisset S, Badiou C, et al. Effect of antibiotics on Staphylococcus aureus producing Panton-Valentine leukocidin. Antimicrob Agents Chemother. 2007;51(4):1515-1519. doi:10.1128/AAC.01201-06
16. Pichereau S, Pantrangi M, Couet W, et al. Simulated antibiotic exposures in an in vitro hollow-fiber infection model influence toxin gene expression and production in community-associated methicillin-resistant Staphylococcus aureus strain MW2. Antimicrob Agents Chemother. 2012;56(1):140-147. doi:10.1128/AAC.05113-11
17. Otto MP, Martin E, Badiou C, et al. Effects of subinhibitory concentrations of antibiotics on virulence factor expression by community-acquired methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother. 2013;68(7):1524-1532. doi:10.1093/jac/dkt073
The Division of Infectious Diseases at the University of Nebraska Medical Center in Omaha, NE is looking to add an ID physician to join our well-established HIV team recognized for providing expert care locally, regionally, and nationally. Enjoy a varied inpatient and outpatient practice mix as part of our patient-centered team. Expect to treat a broad pathology with varied complexity in this position. If you are looking for a position in a robust HIV Program that offers you the ability to provide comprehensive care to a diverse patient population, look no further. Work with phenomenal physicians, nurse practitioners, pharmacists, nurses, social workers, case managers, and exceptional support staff.
These are just 4 members of the larger UNMC HIV team. Check them out here!
This position also includes opportunities to initiate and participate in research activities and engage in the training of fellows, residents, medical students and other interprofessional students.
Know the perfect person for this opportunity? Please spread the word via twitter or with the following application links: HEC, IDSA.
The content below was provided byJocelyn Herstein, an assistant professor at UNMC and Director of International Partnerships and Programs with the National Emerging Special Pathogens Training and Education Center. She led a recently published study, collaborating with UNMC ID faculty Drs. Angela Hewlett and James Lawler.
What prompted this study?
Emerging infectious disease events require a rapid response from health systems; however, evidence-based consensus guidelines are generally absent early in emergency health events.
What does the GIDPN do?
In 2017, the Global Infectious Disease Preparedness Network (GIDPN) was formed by 5 high-level isolation units spanning 3 continents. In the early weeks of the COVID-19 pandemic, when information on the novel disease was frequently evolving and evidence-based guidelines were absent, the GIDPN was leveraged to rapidly exchange information, approaches, and experiences between the five units.
What is the take home message?
The networking facilitated by GIDPN allowed for rapid epidemiological and clinical decision-making in a local context. Shared knowledge led to earlier adoption of some treatment modalities as compared to most peer institutions and to implementation of protocols prior to incorporation into national guidelines. Networking of these specialized high-level isolation units have a role in enhancing preparedness for and response to future epidemics/pandemics.
Jocelyn Herstein, PhD, MPH pictured left, led this project. She is assistant professor at UNMC and Director of International Partnerships and Programs with the National Emerging Special Pathogens Training and Education Center.
Citation: Herstein JJ, Lowe JJ, Wolf T, Vasoo S, Leo YS, Chin BS, Shen Y, Hewlett AL, Lawler JV. Leveraging a Preexisting Global Infectious Disease Network for Local Decision Making During a Pandemic. Clin Infect Dis. 2022 Mar 1;74(4):729-733. doi: 10.1093/cid/ciab660. PMID: 34318871; PMCID: PMC8406886.
Freezing seafood before preparation of sushi is recommended for elimination of certain parasites, but many worry about ruining the taste. Is there any evidence for lower quality in previously frozen seafood? Iwata et. al. investigates.
What does clinical infectious disease research have to offer the culinary world? The answer involves sushi, a freezer, and “a randomized double-blind trial with sensory evaluation using discrimination testing”.
In a recent article published in the journal Clinical Infectious Diseases, Kentaro Iwata and others aimed to disprove the notion that previously frozen seafood is less palatable than fresh seafood when prepared into sushi. Using 120 medical student volunteers and a recruited sushi chef, this group conducted a double-blind taste test of fresh and previously-frozen sushi ingredients. They found that participants were unable to distinguish between the two types of sushi.
This work may help dispel the belief that frozen mackerel and squid tastes worse than fresh fish. This is an important step towards the prevention of gastric anisakidosis caused by a parasite commonly found in fresh seafood. This infection, while usually self-limited and not life threatening, presents with excruciating stomach pain. In fact, the European Union requires and United States FDA recommends freezing these fish before preparation, effectively removing the risk of infection.
The SHEA Spring conference starts tomorrow; here is your guide on where to find UNMC ID throughout the conference!
Invited Training Course Workshop Lectures
Tuesday, April 12th from 10:00am – 10:15am: SHEA/CDC Training Course in Healthcare Epidemiology as presented by our own Kari Simonsen.
Tuesday, April 12th from 2:45pm-3:15pm: Case Studies in Pediatric Infection Control (panel discussion) also with Kari Simonsen (among others).
Dr. Simonsen is also one of the session co-chairs of the SHEA/CDC Training Course in Healthcare Epidemiology!
Invited Lectures in Main Conference
Wednesday, April 13th from 10:00am-12:00pm: Unlocking JEDI Status in the Antimicrobial Stewardship Workforce presented by Jasmine R Marcelin (in session Diversity, Equity, Inclusion, and Access in Antimicrobial Stewardship, Hospital Epidemiology and The Public Health Workforce)
Thursday, April 14th from 2:45 PM – 4:00 PM: Don’t just Publish a Paper – #SoMe Your Story presented by Jasmine R Marcelin (in session Getting your message out to the masses: Understanding the promise and pitfalls of various dissemination methods)
Oral Abstract Presentations
Thursday, April 14th from 8:00am-9:30am: Nosocomial Outbreak of Delta Variant SARS-CoV-2 on a Liver Transplant Unit: A Complex Epidemiologic and Genomic Investigation by 2nd year UNMD ID Fellow Jonathan Ryder (R) and co-authored/mentored by Trevor Van Schooneveld (L). Other authors on this work include Baha Abdalhamid, Macy Wood, Rick Starlin, Gayle Gillett, Teresa Balfour, Libby Pflueger, and Mark E. Rupp.
Follow the conference on Twitter using the hashtag #SHEASpring2022 for meeting updates & highlights.
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