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The Increasing Threat of Antibiotic Resistance

Feb 24, 2016

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The Increasing Threat of Antibiotic Resistance. Shira Doron, MD Assistant Professor of Medicine Division of Geographic Medicine and Infectious Diseases Tufts Medical Center Boston, MA Consultant to Massachusetts Partnership Collaborative:  Improving Antibiotic Stewardship for UTI. - PowerPoint PPT Presentation

Antibiotic stewardship and beyond

The Increasing Threat of Antibiotic ResistanceShira Doron, MDAssistant Professor of MedicineDivision of Geographic Medicine and Infectious DiseasesTufts Medical CenterBoston, MA

Consultant to Massachusetts Partnership Collaborative:Improving Antibiotic Stewardship for UTI

1ObjectivesThe attendee will:Understand the nature of the antibiotic resistance crisisUnderstand the link between antibiotic use and the development of resistant infections, including C diff.Understand the importance of differentiating between colonization and infection in ensuring prudent use of antibiotics.

2Antibiotics in Long Term Care:why do we care?Antibiotics are among the most commonly prescribed classes of medications in long-term care facilitiesUp to 70% of residents in long-term care facilities per year receive an antibioticIt is estimated that between $38 million and $137 million are spent each year on antibiotics for long-term care residentsAs much as half of antibiotic use in long term care may be inappropriate or unnecessary

3The importance of prudent use of antibiotics

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Bad Bugs No Drugs55The drug development pipeline for antibacterials

66A Balancing ActAppropriate initial antibiotic while improving patient outcomes and healthcare Antimicrobial Therapy 7Unnecessary Antibiotics, adverse patient outcomes and increased cost7Antibiotic treatment of nosocomial pneumonia is a balancing act. Clinicians need to treat patients with these potentially life-threatening infections with an appropriate initial antimicrobial regimen while also trying to minimize the emergence of resistant pathogens.What is Antimicrobial Stewardship?Antimicrobial stewardship involves the optimal selection, dose and duration of an antibiotic resulting in the cure or prevention of infection with minimal unintended consequences to the patient including emergence of resistance, adverse drug events, and costDellit TH, et al. CID 2007;44:159-77, Hand K, et al. Hospital Pharmacist 2004;11:459-64Paskovaty A, et al IJAA 2005;25:1-10Simonsen GS, et al Bull WHO 2004;82:928-34Ultimate goal is improved patient care and healthcare outcomes88

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1412 studies in North America:1.8-13.5 infections per 1000 resident-care daysRate of death from infection 0.04-0.71 per 1000 resident-care days15

16The burden of infection in long-term care

17Why focus on long term care?Many long-term care residents are colonized with bacteria that live in and on the patient without causing harmProtocols are not readily available or consistently used to distinguish between colonization and true infectionSo, patients are regularly treated for infection when they have none30-50% of elderly long-term care residents have a positive urine culture in the absence of infection18Why focus on long term care?When patients are transferred from acute to long-term care, potential for miscommunication can lead to inappropriate antibiotic useElderly or debilitated long-term care residents are at particularly high risk for complications due to the adverse effects of antibiotics, including Clostridium difficile infection19Antibiotic misuse adversely impacts patientsGetting an antibiotic increases a patients chance of becoming colonized or infected with a resistant organism.20Association of vancomycin use with resistance

(JID 1999;179:163)21Annual prevalence of imipenem resistance in P. aeruginosa vs. carbapenem use rate

45 LTACHs, 2002-03 (59 LTACH years)Gould et al. ICHE 2006;27:923-5r = 0.41, p = .004 (Pearson correlation coefficient)22CaseAn 82-year-old long-term care resident has a fever and a productive coughHe has no urinary or other symptoms, and a chronic venous stasis ulcer on the lower extremity is unchangedA pan-culture is initiated in which urine is sent for UA and culture, sputum and blood are sent for culture, and the ulcer on the leg is swabbed

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A CXR is done and is negativeThe urinalysis has 3 white blood cellsUrine culture is positive for >100,000 CFU of E coliSputum gram stain has no PMNs, no organismsSputum grows 1+ Candida albicansWound culture grows VRE24

The patient is started on cipro for the E coli in the urine, linezolid for the VRE in the wound, and fluconazole for the Candida in the sputumTwo weeks later the patient has diarrhea and C. diff toxin assay is positive

25The only infection this patient ever had was a viral URI

26Colonized or Infected:What is the Difference?People who carry bacteria or fungi without evidence of infection are colonizedIf an infection develops, it is usually from bacteria or fungi that colonize patientsBacteria or fungi that colonize patients can be transmitted from one patient to another by the hands of healthcare workersThere is no need to treat for colonization2727People who carry bacteria without evidence of infection are colonized.If an infection develops, it is usually from bacteria that colonize patients.Bacteria that colonize patients can be transmitted from one patient to another by the hands of healthcare workers.

The Iceberg Effect

InfectedColonized2828 This iceberg graphically represents colonization versus infection. Those patients that are infected with an organism represent just the tip of the iceberg of patients that are colonized or infected. Just because a patient is not infected, or showing signs of infection, does not mean that they do not carry organisms that could be transferred to another patient if proper hand hygiene and other infection control precautions are not taken.What could have been done differently?Understanding the difference between colonization and infectionNo (or few) WBCs in a UA = no UTIIn the absence of dyspnea, hypoxia and CXR changes, pneumonia is unlikelyCandida is an exceedingly rare cause of pneumoniaWounds will grow organisms when cultured- infection can only be determined clinically

2910 clinical situations in long term care in which antibiotics are often prescribed but rarely necessaryKhandelwal et al. Annals of Long Term Care 2012: 20 (4)30Urinary tract conditions1. Positive urine culture in an asymptomatic patient2. Urinalysis or culture for cloudy or malodorous urine3. Non-specific symptoms or signs not referable to the urinary tract31

Respiratory tract conditions

4. Upper respiratory tract conditions5. Bronchitis absent of COPD6. Suspected or proven influenza without a secondary infection7. Respiratory symptoms in a terminal patient with dementia32

Skin wounds

8. Skin wounds without cellulitis, sepsis or osteomyelitis9. Small localized abscess without significant cellulitis10. Decubitus ulcer in a terminal patient33UTIs in Long Term Care Residents34Microbiology in Nursing HomesNew Haven, CT 5 Nursing Homes May 2005-2007551 patients, presumed UTI

Das R et al. ICHE 2009;30(11):1116-1119.35Das ICHE Nov 200935Antimicrobial Susceptibilities from Nursing Home Residents in New Haven, CT

Das R et al. ICHE 2009;30(11):1116-1119.36AntibiogramHelps to determine best choices for empiric therapy

37Helps with empiric choices, but still need to take into account the clinical pictureMostly concerned about Gram-negative bacteriaFor example for Bactrim for acute cystitis (TRIM-SULFA), if local resistance rates of uropathogens causing UTI do not exceed 20% (or if sensitivity of organism know). Threshold of 20% is based on expert opinion derived from clinical, in vitro and mathematical modeling studies.

BUT for pyelonephritis, threshold is lower, if 10% resistance to cipro, expert opinion recommends additional or alternative agent

Antimicrobial PrescribingEmpiric Initial administration of an antibiotic regimen Goal: improve outcome while minimizing potential to promote resistanceDefined or Targeted Modification of antimicrobial therapy once the cause of infection is identified Goal: select the narrowest spectrum agent possibleTherapy may also be discontinued if the diagnosis of infection becomes unlikely3838Broad-spectrum is defined as covering the most likely pathogens.Targeting, de-escalating and discontinuing antibiotics The empiric regimen is very often NOT the regimen that should be continued for the full treatment course

GET CULTURES and use the data to target therapy using the most narrow spectrum agent possible

Take an Antibiotic Time Out reassess after 48-72 hours3939Culture DataCollect date: 04/15/12 08:35 Result Date: 04/17/12 09:33

SPECIMEN DESCRIPTION : URINE CLEAN CATCH/MIDSTREAM

CULTURE : >100,000 COL/ML ESCHERICHIA COLI

ORGANISM >100,000 COL/ML ESCHERICHIA COLI

AMPICILLIN RESISTANTAMPICILLIN/SULBACTAM INTERMEDIATEAMOXICILLIN/CLAVULAN SUSCEPTIBLECEFAZOLIN SUSCEPTIBLECEFEPIME SUSCEPTIBLECEFTRIAXONE SUSCEPTIBLECIPROFLOXACIN SUSCEPTIBLEERTAPENEM SUSCEPTIBLEGENTAMICIN SUSCEPTIBLELEVOFLOXACIN SUSCEPTIBLEMEROPENEM SUSCEPTIBLENITROFURANTOIN SUSCEPTIBLEPIPERACILLIN/TAZOBAC SUSCEPTIBLETRIMETH/SULFAMETHOX SUSCEPTIBLETETRACYCLINE SUSCEPTIBLE

40Help with narrowing/finalizing therapy40Choosing the perfect antibioticEmpiric:Needs to get to the site of infectionPatients microbiology and antibiotic historyMinimize adverse effectsOther medical problems (renal insufficiency, C.diff, etc)Avoid drug interactionsAllergyThreshold for failureAntibiogram41Choosing the perfect antibioticTargetedTreat specific organismNarrowest spectrum possibleComplianceCostOral option?

42Take Home PointsAntibiotics are a shared resource and becoming a scare resourceAppropriate antibiotic use is a patient safety priority Know the difference between colonization and infectionTo combat resistance: Think globally, act locally

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