Guidelines for Antibiotic Prophylaxis

Rachel Miller, M.D.

Clinical Professor Dept. of Internal Medicine
April 27, 2012

Areas of Focus
Antibiotic prophylaxis for infective endocarditis Antibiotic prophylaxis for individuals with prosthetic joints Antibiotic use for open wounds

Objectives
Review and apply the new AHA practice guidelines for the prevention of infective endocarditis. Discuss the current recommendations for the prevention of prosthetic joint infections. Identify the risk factors for infection after traumatic skin lacerations and the scenarios where antibiotic prophylaxis is indicated. Evaluate the risk of administering prophylactic antibiotics vs. the scientific evidence for benefit into clinical decision-making.

Guidelines for the Prevention of Infective Endocarditis

Theoretical Basis for Endocarditis Prophylaxis

Pathogenesis of endocarditis:
Formation of non-infected thrombus on an abnormal endothelial surface Secondary infection of this thrombus occurs during transient bacteremia with bacterial adherence Proliferation of bacteria within thrombus with vegetation formation

Prevention/prompt tx of transient bacteremia interrupts this sequence

The History of Antibiotic Prophylaxis to Prevent Endocarditis

2007: Newest revision by AHA in conjunction with ADA, IDSA, AAP 1990 1984 1977 Several iterations of AHA guidelines documents 1972 1965 1957 1955: 1st AHA document on IE prophylaxis 1930: Antibiotic prophylaxis for IE becomes standard practice

Time for a Change.

PRACTICE GUIDELINE: FOCUSED UPDATE ACC/AHA 2008 Guideline Update on Valvular Heart Disease: Focused Update on Infective Endocarditis
A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines
Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons

Rationale for change:

Only an extremely small # of cases may be prevented by antibiotic prophylaxis, even if it was 100% protective IE is more likely to result from frequent exposure to random bacteremias associated with daily activities. Antibiotic-associated adverse effects exceed the benefits of prophylaxis

Does antibiotic prophylaxis really prevent endocarditis?

It does in animal models of valvular heart disease with induced bacteremia. It can reduce bacteremia associated with dental procedures. No study in humans has definitively demonstrated IE prevention after invasive procedures. Prophylaxis failures occur.

Bacteremia is a Common Occurrence in Daily Life

Incidence of bacteremia after various procedures
Dental extraction Chewing Tooth brushing (higher if sonicating) EGD Colonoscopy Urethral dilatation Urethral catheterization Nasotracheal suctioning 18-85% 32-88% 20-40% 8-12% 0-10% 18-33% 8% 16%

Estimated 5370 min (~90 hrs) of bacteremia/mo in dentulous persons who chew and practice standard oral hygiene

Estimated Endocarditis Risk Associated with Dental Procedures

Underlying Heart Dx
None Congenital Heart Dx Rheumatic Heart Dx Prosthetic Heart Valve Previous Endocarditis # Dental Procedures/ 1 Case of Endocarditis 14 million 475,000 142,000 114,000 95,000

AHA Guidelines, Circulation, May 2007

 the focus on the frequency of bacteremia associated with a specific dental procedure and the AHA guidelines for prevention of IE have resulted in an overemphasis on antibiotic prophylaxis and an under-emphasis on maintenance of good oral hygiene and access to routine dental care, which are likely more important in reducing the lifetime risk of IE than the administration of antibiotic prophylaxis for a dental procedure.

AHA Guidelines, Circulation, May 2007

The Major Changes in the Updated AHA Guidelines

Prophylaxis is aimed at those at highest risk for an adverse outcome of IE, rather than solely based on an increased lifetime risk of IE. Significant simplification of conditions and procedures that warrant prophylaxis. Overall, more evidence based, rather than opinion based.

Conditions of Highest Risk

Included Prosthetic heart valves Prior endocarditis Cyanotic heart disease
Unrepaired Repaired congenital heart dx with prosthetic material or device x6 mo Repaired with residual defects

Not included Bicuspid aortic valve Acquired aortic or mitral valve disease
MVP with regurgitation Prior valve repair

Heart transplant with valvulopathy

Hypertrophic cardiomyopathy with latent or resting obstruction

AHA Guidelines, Circulation, May 2007

Procedures Warranting Antibiotic Prophylaxis to Prevent IE

Dental Procedures:
All dental procedures that involve manipulation of gingival tissue, periapical region of the teeth, or perforation of the oral mucosa.
Dental extractions Periodontal procedures Endodontic instrumentation Prophylactic cleaning Initial placement of orthodontic bands (not brackets)

Respiratory procedures:
Procedures involving incision/ biopsy of the mucosa
Removal of tonsils/ adenoids TBBX but NOT bronchoscopy only

GU procedures:
ONLY during active enterococcal infection

GI procedures:
NO LONGER INCLUDED
AHA Guidelines, Circulation, May 2007

IE Prophylaxis Regimens for Dental Procedures

Situation
Oral
Unable to take oral meds

Agent
Amoxicillin Ampicillin Cefazolin or Ceftriaxone Cephalexin Clindamycin Azithromycin Cefazolin or Ceftriaxone Clindamycin

Adults*
2g 2 gm IM/IV 1 gm IM/IV 2 gm 600 mg 500 mg 1 gm IM/IV 600 mg IM/IV

Children*
50 mg/kg 50 mg/kg IM/IV for all 50 mg/kg 20 mg/kg 15 mg/kg 50 mg/kg IM/IV 20 mg/kg IM/IV

PCN Allergyoral PCN Allergyunable to take oral meds

* Single dose given 30-60 min before procedure

Endocarditis and Pharyngitis

Should patients with valvular heart disease and pharyngitis be treated more readily with antibiotics? Proposed rationale #1:
Streptococci are a common cause of IE, thus antibiotic therapy will prevent bacteremia and subsequent IE.

The Facts:
Streptococci account for 60-80% of IE cases Group A Streptococci (GAS) IE is extremely rare Ratio of IE to non-IE bacteremia cases for GAS is 1:32 Conclusion: Persons with pharyngitis and valvular heart dx do not require Abx tx on the basis of preventing GAS IE.

Should patients with valvular heart disease and pharyngitis be treated more readily with antibiotics?
Proposed rationale #2:
Streptococcal pharyngitis can predispose to rheumatic fever and subsequent rheumatic heart disease, which may make underlying valvular disease worse.

The facts:
GAS pharyngitis is a known trigger of rheumatic fever (RF) Recurrent GAS pharyngitis can lead to recurrent episodes of RF and eventual valvular heart disease (<25%) Prolonged PCN prophylaxis following an episode of RF can prevent relapses and progressive valvular destruction Conclusion: Prolonged PCN prophylaxis, not repeated PCN courses, for pharyngitis is the standard of care to prevent recurrent RF.

Infective Endocarditis Prophylaxis

Summary of Major Points
Only an extremely small # of IE cases will likely be prevented by antibiotic prophylaxis for procedures (dental). The latest AHA guidelines have significantly trimmed the indications for antibiotic prophylaxis. The treatment approach to GAS pharyngitis should not be altered on the basis on underlying valvular heart disease.

Antibiotic Prophylaxis for Patients with Total Joint Replacements

The Clinical Landscape

More than 750,000 total joint arthroplasties done annually in the US As the US population ages, demand is expected to rise by 200-600% over the next 25 yrs Prosthetic joint infections (PJIs) cause significant morbidity and mortality Attributable cost of a single PJI episode is 3-4x the cost of the primary arthroplasty (usually >$50,000)

The Gray Zone of Antibiotic Prophylaxis to Prevent PJIs

Purposefully omitted from AHA IE prevention guidelines The analogy of PJIs with IE is invalid No convincing evidence that prophylaxis during dental procedures prevents PJIs

Advisory Statement of the ADA and AAOS

Oral bacteremias induced by daily events are more common than dental-treatment induced Critical period for PJI is up to 2 yrs after surgery No prophylaxis is needed for patients with pins, screws and plates Good dental health PRIOR to joint replacement highly encouraged
JADA 134:895, 2003

Summarized Recommendations from the ADA/ AAOS Advisory Statement

Antibiotic prophylaxis is not routinely indicated for most dental patients with TJRs. However, it is advisable to consider pre-medication in a small number of patients who may be at potential increased risk.* High risk ~ <2 yrs post-op, immunocompromised, significant co-morbidities Similar dental procedures and antibiotic recommendations as AHA guidelines
* Based on expert opinion. No established studies showing an association of PJIs with dental procedures. JADA 134:895, 2003

.but the debate continued.

2009 Information Statement from AAOS safety committee

Prior 2 yr designation now removed

http://www.aaos.org/about/papers/advistmt/1033.asp

Dental Procedures & PJIs

Counterpoint #1
Study Design:
Single center, prospective case-control study of 339 inpatients w/wo hip or knee PJI from 2001-2006 at the Mayo Clinic

Findings:
No risk of PJIs in pts undergoing high or low risk dental procedures without antibiotic prophylaxis Antibiotic prophylaxis did not the risk of PJIs No difference with subset analysis of PJIs of potential dental/oral origin Trend toward PJIs in pts with >1 dental hygiene visit

Conclusions:
Data refute the AAOS recommendation of universal antibiotic prophylaxis for dental procedures in pts with arthroplasties
Berbari EF, Clin Inf Dis 50:8, 2010

Dental Procedures & PJIs

Counterpoint #2
Study Design:
Data from Medicare Current Beneficiary Survey (1997-2006) 1000 participants with JR, identified those with PJI (42 pts) and compared them with matched controls

Findings:
No association between dental procedures and PJIs in either time-to-event analysis nor the case-control analysis Trend toward more dental procedures in preceding 90 days in control pts than those with PJIs

Conclusions:
Dental procedures not associated with a higher risk of PJIs The 2009 AAOS Information Statement should be reconsidered
Skaar DD, JADA 142:1343, 2011

The Final Recommendations Remain Gray.

Not intended as standard of care or substitute for clinical judgment. Practitioners must exercise their own clinical judgment in determining whether or not antibiotic prophylaxis is appropriate.

http://www.aaos.org/about/papers/advistmt/1033.asp JADA 134:895, 2003

Antibiotic Prophylaxis for Traumatic Lacerations & Open Wounds

Background
Lacerations and open wounds are the 3rd most commonly encountered problems in the ED
Account for 8% of the 95 million ED visits in US/ year

Variable risk of infection depending on type of injury

Incised, puncture, bites, abrasions

Common Goals of Treatment: Avoiding infection Optimal functional and cosmetic result

General Principles of Initial Traumatic Wound Management

Wound cleansing
Use tap water or normal saline For contaminated wounds, use pressure irrigation

Keep the wound moist

Topical antimicrobial agents Cover with an occlusive dressing

Ascertain tetanus immunization status

Dire DJ, Acad Emer Med 2:4, 1995 Singer AJ, NEJM 359:10, 2008

Risk Factors for Infection in Patients with Traumatic Lacerations

Study Design:
Cross-sectional, prospective Data sheets collected at time of repair & suture removal

Study Population:
Univ Med Center at Stony Brook, 1992-1996 All pts with traumatic lacerations eligible, without standardizing wound tx

Results:
5521 pts enrolled, 194 infections (3.5%) over 4 yrs Mean time of presentation: 2.1 (+/- 3.6 hrs after injury) Foreign body/bite wounds accounted for <20% Most had single layer repairs 14% treated with systemic antibiotic prophylaxis
Hollander JE, Acad Emer Med 8:716, 2001

Risk Factors for Infection in Patients with Traumatic Lacerations

Characteristic Risk of Infection
Age* Diabetes* Longer, wider, deeper, jagged* Foreign body identified* Visible contamination OR 1.01 per yr of life 3.9 1.6-1.8 2.9 1.8 0.3 0.5

Relative Risk of Infection

Risk of Infection
Head/scalp wounds* Blunt mechanism of injury

* Remained significant by multivariate modeling

Adjustment for systemic antibiotic prophylaxis did not alter results Hollander JE, Acad Emer Med 8:716, 2001

High-Risk Wounds where Antibiotic Prophylaxis Recommended

Significant immunocompromise
DM, PVD, AIDS, lymphedema, steroid use

Open fractures or wounds into joints Wounds involving tendons or cartilage Gross contamination & cannot be adequately cleaned Puncture or crush injuries Bite wounds Oral wounds >18 hr delay in presentation
Moran GJ, Infect Dis Clin No Amer 22:117, 2008

Antibiotic Recs for High-Risk Wounds

Clinical Scenario Most settings Intra-oral wounds Bite wounds Grossly contaminated or devitalized Recommended Antibiotic 1st generation cephalosporin Penicillin Amoxicillin-clavulanate

Additional Points:
Parenteral antibiotics not shown to more effective than oral antibiotics It is not necessary to include activity against CA-MRSA For most cutaneous wounds, 24 hrs of antibiotics after wound closure is sufficient
Moran GJ, Infect Dis Clin No Amer 22:117, 2008

Plantar Puncture Wounds

Superficial infection rate is 210%
Staph, Strep Pseudomonas (tennis shoes)

risk for deep, forefoot wounds, delayed presentation No randomized trials have evaluated the benefits of prophylactic Abx Prospective, observational study suggests cleansing alone likely adequate with close f/u
Singer AJ, NEJM 359:1037, 2008

Mammalian Bite Wounds

Risk of Infection
Dog: 3-18%, usu. lacerations Human: up to 50%, MC joints Cat: 28-80%, puncture

Bacteriology
Primarily mixed anaerobes and aerobes Cats: Pasteurella multocida Dogs: P. multocida, Capnocytophaga canimorsus Humans: HBV, HIV
Singer AJ, NEJM 359:1037, 2008 Moran GJ, Infect Dis Clin No Amer 22:117, 2008

Mammalian Bite Wounds

Rec prophylactic antibiotics
Amoxicillin-clavulanate Cipro + clindamycin (adults) Cipro + TMP-SMX (peds)

Duration: 3-5 days Systematic data review concludes benefit of antibiotic prophylaxis only for hand bites and cat/human bites
Singer AJ, NEJM 359:1037, 2008 Moran GJ, Infect Dis Clin No Amer 22:117, 2008

One More Point.

The Negative Aspects of Antibiotic Prophylaxis
Non-fatal adverse reactions
Rash, GI sxms, C. difficile colitis Stevens-Johnson syndrome, TENS

Fatal anaphylactic reactions

Est. 15-25 rxns/ 1million treated with PCN

Drug interactions Adding to the resistance burden The hassle factor

A large # of pts need to be treated to prevent a single case of infection. The risk of antibiotic associated adverse events exceeds the benefit, if any.

Take Home Points

The data on which antibiotic prophylaxis recommendations are based is limited and inconclusive. Less is (likely) more Antibiotic prophylaxis guidelines are only guidelines. They are no substitute for clinical judgment.