Clinical Inertia. Infectious Disease Update: Clostridium Difficile and Lyme Disease. Objectives. Guidelines for Antimicrobial Stewardship.

Transcription

1 Infectious Disease Update: Clostridium Difficile and Lyme Disease Jody Agins MSN, RNP, FNP/GNP-BC Collaborative Medical Provider Group PLLC Objectives Recognize the growing incidence, virulence, resistance of C difficile & newest treatment guidelines Discuss new guideline recommendations within Lyme Disease List 3 antibiotic treatments for C difficile and Lyme Disease List strategies for C-Diff & Lyme Disease that will decrease exposure, risk & re-infection Disclosures This speaker has no financial or other conflicts of interest to disclose Guidelines for Antimicrobial Stewardship SHEA Society for Healthcare Epidemiology of America IDSA Infectious Diseases Society of America CDC, Antibiotic Use & CDiff 2014 CDC analysis of data regarding antibiotic prescribing in hospitalized patients Estimated: 30% reduction in use of broad-spectrum antibiotics would result in a 26% reduction in CDIs Clinical Inertia Jody Agins, MSN, RNP, FNP/GNP-BC

2 Clostridium Difficile Disease C difficile Carriage & Transmission Adults in hospitals & long-term care facilities 20 to 50 % Carrier rate among healthy adults 3 % Those with negative admission stool cultures who become infected during hospitalization 20 % C difficile Carriage & Transmission Even asymptomatic individuals Shed pathogenic organisms Serve as reservoir for environmental contamination to other hospitalized patients Highly transmissible Can culture from any surface, including hands, clothing, and stethoscopes of healthcare workers Newly exposed patients develop more frequently than colonized patients Any antibiotic can predispose to colonization metronidazole and vancomycin Clinical Presentation Almost 50 % may not have typical symptoms Diarrhea Cramps, fever, malaise, anorexia Abdominal pain Ileus Little to profound leukemoid reactions Severe hypoalbuminemia Septic shock Toxic megacolon Pathophysiology Colonization, alteration of flora, organism growth Toxin A Enterotoxin Tissue damage, fluid secretion, inflammation Not necessary for virulence Less potent than B Cytotoxin B 1000 times more potent than A Activate release of cytotoxins from monocytes Newer Resistant C Diff Anaerobic, gram positive, spore-forming bacillus Annually in US > 14,000 die of C. difficile Hypervirulent strain (BI/NAP1/027) Cause of outbreaks in facilities since 2001 More resistant to antibiotics Associated with more severe disease About 1/3 of US cases Jody Agins, MSN, RNP, FNP/GNP-BC

3 C Difficile CDC Reports Approximately 500,000 cases annually 2/3 result from hospitalization or facility exposure 1/3 from community Annual US deaths ,000 80% of deaths Age > 65 1 of 9 patients over 65 with C difficile dies within 30 days of diagnosis Risk Factors Inflammatory bowel disease Acid suppressive agents H2-blockers PPIs Exposure to antibiotics not seen as frequently BUT includes Cephalosporins, Amoxicillin Clavulanate, Quinolones, Metronidazole, Vancomycin Immunosuppression / chemotherapy Age >65-70% 80% of cases Chronic Renal Failure Treatment Guidelines New Guidelines: 2017 SHEA: Society for Healthcare Epidemiology & IDSA Published Infection Control & Hospital Epidemiology May 2010 ACG American College of Gastroenterology ESCMID European Society of Clinical Microbiology and Infectious Diseases Guidelines Testing should be on diarrheal stools only Stool from asymptomatic pts not clinically useful Test of cure not recommended ** Polymerase chain reaction (PCR) Rapid, sensitive, specific Enzyme immunoassay (EIA) testing for A&B Less sensitive although rapid Probiotics NOT recommended to prevent primary C Diff Discontinue antimicrobial agent asap Guidelines Avoid antiperistaltic agents Opioids?? Imodium, etc If stool toxin assay negative, individualize decision to treat anyway Start empirical treatment if suspected Jody Agins, MSN, RNP, FNP/GNP-BC

4 Guidelines Supportive care Hydration Electrolytes No milk products Skin care Treatment: Mild to moderate Metronidazole 500 mg by mouth TID for days If intolerant to metronidazole: vancomycin 125 mg by mouth QID for days If significant risk of recurrence Vancomycin 125 mg by mouth, four times daily, for days Fidaxomicin, 200 mg by mouth, twice daily, for 10 days Treatment: Severe Vancomycin 125 mg by mouth four times daily, for days If significant risk of recurrence Fidaxomicin, 200 mg by mouth, twice daily, for 10 days Treatment: Severe Complicated Vancomycin 125 mg or 500 mg (if ileus, toxic colon, or significant abdominal distension) by mouth, four times daily AND / OR vancomycin 500 mg per rectum four times daily (If ileus, toxic colon, or significant abdominal distension) PLUS metronidazole 500 mg intravenously Q 8 hr Surgical consultation / management If significant risk of recurrence Fidaxomicin, 200 mg by mouth, twice daily, for 10 days Fidaxomicin Macrocyclic antibiotic: bactericidal Metronidazole & vancomycin are bacteriostatic Narrower antimicrobial spectrum -less disruption of normal colonic anaerobic microflora Has prolonged post-antibiotic effect (~10 hours) allowing for twice-daily dosing Treatment of initial episode associated with lower incidence of recurrent CDI than vancomycin (15 % vs 25 %) 200 mg twice daily X 10 days With or without food October 2016 FDA Approval Bezlotoxumab (Zinplava) Human monoclonal antibody that binds to C difficile toxin B & neutralizes its effects Monocolonal Antibodies For C Difficile Therapy (MODIFY) I and MODIFY II studies Single dose (in conjunction with antibiotics) of 10 mg/kg IV over 60 minutes For high risk Over age 65, recent CDI (within 6 months), prior recurrent CDI, compromised immunity, severe CDI, or infection with a hypervirulent, binary toxin positive strain Jody Agins, MSN, RNP, FNP/GNP-BC

5 Other Treatment Approaches Cholestyramine resin (1-4gm daily to BID) IgG infusion at dose of 200 to 300mg/kg Fecal Microbiota Transplant (FMT) Fecal Microbiota Transplant (FMT) Over 50 % of patients would rather have this than medication therapy No contraindications 80% 90% cure rate for relapse CDI Younger donors tend to donate stool samples for their older relatives while older donors commonly donate specimens for their spouses Guidelines do not suggest an upper limit of age to exclude donors for the purpose of FMT Fecal Microbiota Transplant (FMT) Prepared feces Usually family member, can be any donor g fresh stool (6-24hrs old) Blended with NS for a total of 500ml Nasogastric or nasojejunal tube, colonoscopy (risk?), enemas, oral capsulized frozen FMT Stool Donor Screening Ova and parasites Stool culture and sensitivity test Generally includes: Salmonella, Shigella, Escherichia coli, Yersinia enterocolitica, and Campylobacter Clostridium difficile toxins A and B Some additionally screen for cryptosporidium antigen and Giardia antigen Stool Donor Exclusions HIV Hepatitis B or C or known exposure within previous year High-risk sexual behaviors Illicit drug use Tattoo or body piercing within previous 6 months Recently incarcerated Traveled to world areas with endemic Chronic constipation Recurrent Clostridium difficile infection Rates of recurrence After 1 st episode 20 % Chronic diarrhea Inflammatory or irritable bowel disease/syndrome History of GI malignancy or known GI polyposis Anything that would affect intestinal microbiota After 1 st recurrence Antibiotics in preceding 45 % 3 months Currently receiving major After two or more recurrences immuno-suppressive medications or systemic 65 % antineoplastic agent 30 Jody Agins, MSN, RNP, FNP/GNP-BC

6 Recurrence First recurrence Repeat same regimen used for initial episode Second recurrence Vancomycin oral pulse or taper only Third recurrence Vancomycin plus fecal microbiota transplant If significant risk of recurrence Fidaxomicin, 200 mg po, twice daily, for 10 days Severe CDI JAMA Retrospective study found no difference in the risk of Clostridium difficile infection (CDI) recurrence among patients treated with vancomycin or metronidazole BUT risk of all-cause 30-day mortality was significantly lower when CDI was treated with vancomycin There was no difference in recurrence rate Second positive laboratory test within 8 weeks of initial diagnosis & treatment Metronidazole (Flagyl) Caution Not recommended beyond first recurrence RT cumulative neurotoxicity After prolonged use (cumulative mg dose) Symptoms resolve usually 3 7 days after use Peripheral; optic; cutaneous Causes cerebellar toxicity Varying degrees: limb & gait ataxia, dysarthria, headache - MRI: T2 high signal lesions also brainstem Hypothesis Axonal swelling RT induced vasogenic edema Suggested Tapering Schedule Week Vanco dose 1 125mg qid 2 125mg bid 3 125mg daily 4 125mg every other day 5 & 6 125mg every 3 days Recurrence: Oral Probiotics Saccharomyces boulardii, 500 mg BID for 4 weeks plus Vancomycin Lactobacillus GG (Lactinex), 1-g packet 4 times a day for 14 days after Vancomycin Other Thoughts Incontinence: securely Depended so as to prevent environmental contamination Antibiotics, antidiarrheal agents used sparingly May lengthen duration, cause complications Fluid replacement, preferably with oral fluids No apple juice or milk products Temporarily eliminate milk products as damage to mucosa may lead to temporary lactose intolerance Jody Agins, MSN, RNP, FNP/GNP-BC

7 Environmental Survival & Contamination Vegetative form survives 15 minutes on dry surfaces in room air Remains viable up to 6 hours on moist surfaces Spores: Highly resistant Drying, heat, chemical & physical agents Can exist for 5 months on hard surfaces One study found spores 49% of rooms occupied with CDI 29% in rooms of asymptomatic carriers 37 Environmental cleaning for C. difficile Use of sporucidal disinfectants for cleaning patient care area and bathroom Daily Focus on high touch areas and commode Household bleach in 1:10 dilution Prepared fresh daily Wipe off prevents residue leading to skin irritation Needs contact time of 10 minutes From the Horse s Mouth: CDC s Web Site After treatment, repeat C. difficile testing is not recommended if symptoms have resolved, as patient may remain colonized Lyme Disease Lyme Disease Time Line 1975 Disease is named after town of Lyme, Connecticut Initially Lyme arthritis Combination cardiac, neurologic & rheumatologic Heart block, meningitis & Bell s palsy 1978 Lyme disease thought to be tick-borne disease 1981 B. burgdorferi identified by Willy Burgdorfer Transmitted by Ixodes ticks Also: Borrelia afzelii & Borrelia garinii Spirochete Antigen Bacteria lipoprotein is neuro toxin Antigens deposited on healthy tissue causes an autoimmune response Jody Agins, MSN, RNP, FNP/GNP-BC

8 Testing Tests are insensitive Negative test result does not mean negative measures response NOT disease May not have been time for antibodies development Immune system may be suppressed Infection with strain the tests don t measure 52% with chronic disease negative by ELISA - positive by Western blot Early Localized Infection 3 30 Days Target Lesion Rash is generally painless Occurs about 80% of infected patients Flu-like symptoms Headache Muscle soreness / Myalgias Fever Malaise Early Disseminated Infection Days - Weeks Migrating pain: muscles, joints, tendons Heart palpitations Dizziness Facial palsy (Bell s) Meningitis Shooting pains Mild encephalitis / Memory Loss Sleep disturbances Mood / Personality changes Late Disseminated Infection After Several Months Profound fatigue Depression Fibromyalgia Encephalomyelitis Weakness in legs / Awkward Gait Facial palsy Uninary Incontinence Schizophrenia / Bipolar disorder / Panic Anxiety / Delusions Delusions / Depression /Cognitive Impairment Arthritis & Painful joints IDSA vs ILADS Guidelines Infectious Disease Society of America Last updated 2006 Antitrust investigation filed International Lyme And Associated Diseases Society - ILAADS Last updated in 2014 Endorsed: National Guidelines Clearinghouse Federal database that provides treatment information to health care professionals & insurance companies Treatment Guidelines: Category 1 Management: Known Ixodes species bite Prompt prophylaxis Doxycycline mg BID: Minimum 20 days: regardless of degree of tick engorgement or infection rate in local tick population Education on prevention of future tick bites, manifestations of Lyme & other Ixodes-borne diseases and manifestations & prevention of antibiotic-associated C. difficile infection Jody Agins, MSN, RNP, FNP/GNP-BC

9 Treatment Guidelines: Category 2 Management: Erythema Migrans (EM) rash May be absent > 50% of Lyme disease cases Recommendation Minimum 4 6 weeks of amoxicillin, cefuroxime (Ceftin) or doxycycline OR minimum 3 weeks of azithromycin Ongoing assessment to detect persistence, progression or relapse of Lyme disease or presence of other tick-borne illnesses. Treatment Guidelines: Category 2 Recommendations Extending treatment in those who remain symptomatic after initial therapy Retreatment of persistent, recurrent or newly developed manifestations Education regarding potential manifestations of Lyme disease & other Ixodes-transmitted infections, as well as manifestations & prevention of antibioticassociated C. difficile infection Treatment Guidelines: Category 3 Management : persistent post-treatment manifestations 4 6 weeks of antibiotics when retreatment is undertaken: antibiotic selection based on several factors Reassessment immediately following initial course of retreatment & basing decisions regarding subsequent modification or discontinuation of treatment on several factors Treatment Guidelines: Category 3 Strongly recommends discussing possibility of antibiotic retreatment with all patients & performing individualized risk-benefit assessments Also including information regarding symptoms of & ways to reduce risk for antibiotic-associated C. difficile Pediatric Dosing Pediatric dosing Amoxicillin 50 mg/kg/day: 3 divided doses, with maximal daily dose 1500 mg Cefuroxime mg/kg/day in two divided doses, with max daily dose of 1000 mg Azithromycin 10 mg/kg on Day 1 then 5 10 mg/kg daily, with max daily dose 500 mg Children Over Age 8 Doxycycline 4 mg/kg/day in two divided doses with max daily dose of 200 mg Higher daily doses of all individual agents may be appropriate in adolescents Jody Agins, MSN, RNP, FNP/GNP-BC

10 Responses to Treatment Modest: Increase dose of original antibiotic or switch to different first-line agent or tetracycline Minimal or absent: Combination of first-line agents, which includes at least one that is able to effectively reach intracellular compartments IM penicillin G benzathine (Bicillin LA) or IV ceftriaxone Retreatment Retreat anyone successfully treated initially but subsequently relapse or have symptoms of disease progression Repeat initial agent Change to another oral agent or start IM penicillin G benzathine, IV ceftriaxone Retreatment Choice is individualized, based on Initial response to treatment Time to relapse or progression Current disease severity Quality of life impairments Retreatment Mild impairments with strong-to-moderate response to initial antibiotic Repeat treatment with same antibiotic Moderate impairments or only modest response to initial antibiotic Switch to different agent or combination of agents Significant impairments and/or minimal or absent therapeutic response Combine oral antibiotics, injectable penicillin G benzathine or IV ceftriaxone (with latter 2 alone or in combination with other agents) Disease Progression Disease progression despite earlier therapy Treat with injectable penicillin G benzathine or IV ceftriaxone, alone or in combination with other antibiotics Treat for length of symptoms, not set time References: C-Diff Clinical Practice Guidelines for Clostridium difficile Infection in Adults: 2010 Update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA) nical%20practice%20guidelines%20for%20c%20diff% 20Infection%20%202010%20update%20by%20SHEA- IDSA.pdf CP.html Jody Agins, MSN, RNP, FNP/GNP-BC

11 References: C-Diff APIC Guide to the Elimination of Clostridium difficile Infections in Healthcare Settings. ance/apiceliminationguides/c.diff_elimination_guide_log o.pdf SHEA: Clostridium difficile in Long Term Care Facilities for the Elderly Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease References: Lyme Disease New Standard Of Care Guidelines for Treating Lyme and Other Tick-Borne Illnesses Released by International Lyme and Associated Diseases Society (ILADS) References: Lyme Disease Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease Jody Agins, MSN, RNP, FNP/GNP-BC