In the Clinic: Evidence Based Management of Infections

Daniel Deck, Pharm.D.

San Francisco General Hospital

Overview

Community-acquired pneumonia

Upper respiratory tract infections

Urinary tract infections

Skin and Soft-tissue infections

Community-acquired pneumonia

Community Acquired Pneumonia (CAP): definition

At least 2 new symptoms

New infiltrate on chest x-ray and/or abnormal chest exam

No hospitalization or other nursing facility prior to symptom onset

Fever or hypothermia Cough

Rigors and/or diaphoresis Chest pain

Sputum production or color change Dyspnea

Diagnosis Chest radiograph – needed in all cases?

Avoid over-treatment with antibiotics

Differentiate from other conditions

Specific etiology, e.g. tuberculosis

Co-existing conditions, such as lung mass or pleural effusion

Evaluate severity, e.g. multilobar

Unfortunately, chest physical exam not sensitive or specific and significant variation between observers Arch Intern Med 1999;159:1082-7

Microbiological Investigation

Sputum Gram stain and cultureRemains somewhat controversial

30-40% patients cannot produce adequate sample

Most helpful if single organism in large numbers

Usually unnecessary in outpatients

Culture (if adequate specimen < 10 squamous cells/LPF; > 25 PMNs/LPF): antibiotic sensitivities

Limited utility after antibiotics for most common organisms

Etiology Clinical syndrome and CXR not reliably predictive

Streptococcus pneumoniae 20-60%

Haemophilus influenzae 3-10%

Mycoplasma pneumoniae up to 10%

Chlamydophila pneumoniae up to 10% “Atypicals”

Legionella up to 10%

Enteric Gram negative rods up to 10%

Staphylococcus aureus up to 10%

Viruses up to 10%

No etiologic agent 20-70%

S. pneumoniae

2/3 of CAP cases where etiology known

2/3 lethal pneumonia

2/3 bacteremic pneumonia

Apx. 20% of cases with pneumococcal pneumonia are bacteremic (variable)

Risk factors include

Extremes of ageAlcoholismCOPD and/or smokingNursing home residence

InfluenzaInjection drug useAirway obstruction*HIV infection

S. pneumoniae – drug resistance

~ 25-35% penicillin non-susceptible by old standard nationwide, but most < 2 g/mL

Using the new breakpoints for patients without meningitis, 93% would be considered susceptible to IV penicillin

Other beta-lactams are more active than pencillin, especially

Ceftriaxone, cefotaxime, cefepime, amoxicillin, amoxicillin-clavulanate

S. pneumoniae – drug resistance Other drug resistance more common with increasing

penicillin minimum inhibitory concentration (MIC)

Macrolides and doxycycline more reliable for PCN susceptible pneumococcus, less for penicillin non-susceptible

Trimethoprim-sulfamethoxazole not reliable

Fluoroquinolones – most S. pneumoniae are susceptible

Clinical failures have been reported

No resistance with vancomycin, linezolid

Risk Factors for Drug-Resistant Pneumococcal Pneumonia

Age < 2 year or > 65 years

-lactam antibiotics within 3 months

Alcoholism

Immunocompromised patients

Multiple comorbidities

Exposure to children in day care centers

Conditions that Increase the Morbidity/Mortality of CAP

COPD

Alcoholism

Leukopenia

Bacteremia

Diabetes mellitus

Renal insufficiency

CHF

CAD

Malignancy

Neurologic disease

Chronic liver disease

Immunosuppression

IDSA Outpatient Empiric Therapy Recommendations

Previously Healthy & Previously Healthy & NONO DRSP Risk FactorsDRSP Risk Factors

DRSP Risk Factors DRSP Risk Factors oror High Level High Level Macrolide Resistance > 25%Macrolide Resistance > 25%

Macrolide (e.g azithromycin)Macrolide (e.g azithromycin)

oror

DoxycyclineDoxycycline

1) Fluoroquinolone1) Fluoroquinolone** oror

2) a 2) a ββ-Lactam-Lactam## plusplus

a Macrolide or Doxycyclinea Macrolide or Doxycycline

*moxifloxacin, gemifloxacin, or levofloxacin (750mg)*moxifloxacin, gemifloxacin, or levofloxacin (750mg)##Amoxicillin 1 gm PO tid or Augmentin® XR 2 gm PO bid are preferred. Ceftriaxone, Amoxicillin 1 gm PO tid or Augmentin® XR 2 gm PO bid are preferred. Ceftriaxone,

cefpodoxime proxetil, and cefuroxime axetil 500 mg PO bid are alternativescefpodoxime proxetil, and cefuroxime axetil 500 mg PO bid are alternatives

We love doxycycline

Adult inpatients June 2005 – December 2010

Compared those who received ceftriaxone + doxycycline to those who received ceftriaxone alone

2734 hospitalizations: 1668 no doxy, 1066 with doxy

Outcome: CDI within 30 days of doxycycline receipt

CDI incidence 8.11 / 10,000 patient days in those receiving ceftriaxone alone; 1.67 / 10,000 patient days in those who received ceftriaxone and doxycycline

Doernberg et al, Clin Infect Dis 2012;55:615-20

Duration of Therapy

5 days should be the minimum duration of therapy

Patients should be afebrile for 48-72 hours

No more than 1 CAP-associate sign of clinical instability (T > 37.8ºC, HR >100, RR > 24, SBP < 90, O2 sat < 90%, pO2 < 60)

Short-Course Therapy

Defined as less than 7 days of therapy

Short course therapy may reduce side effects, cost, and resistance

Azithromycin has been used for 3-5 days

Ceftriaxone, amoxicillin, and fluoroquinolones have been used for 5 days

Reasons for Inadequate Response to Empiric Therapy

Inadequate Antibiotic Selection

Unusual Pathogens

Complications of Pneumonia

Incorrect Diagnosis

Drug-resistant organisms

Upper Respiratory Tract Infections

Upper respiratory tract infections

Rhinosinusitis

~13 million outpatient visits per year

Viral causes >>>> bacterial

Minimal to NO benefit from antibiotics given for short duration of disease

Xray/CT not helpful in distinguishing cause

Rhinosinusitis diagnosis

Major Criteria Purulent anterior nasal discharge

Purulent posterior nasal discharge

Nasal congestion or obstruction

Facial congestion or fullness

Facial pain or pressure

Hyposomia or anosmia

Fever (acute disease)

Minor Criteria Headache

Ear pain, pressure, or fullness

Halitosis

Dental pain

Cough

Fever (chronic disease)

Fatigue

Need at least 2 major or 1 major and ≥ 2 minor criteria

IDSA guidelines: rhinosinusitis

Antibiotics may be helpful if….

1. Persistent signs/symptoms > 10 days

2. Severe symptoms

Fever > 39C

Purulent nasal drainage for 3 consecutive days

Facial pain

3. Biphasic illness

IDSA guidelines: rhinosinusitis

Recommened 1st line therapy =

Amoxicillin/clavulante (standard dose)

Consider high dose (XR formulation) with severe disease, elderly, recent antibiotic use or hospitalization

Alternatives: doxycycline, levofloxacin

Treatment duration: 5-7 days

Not Recommended

• Macrolides

• TMP/SMX

• Oral cephalosporins

• Routine MRSA coverage

IDSA guidelines: rhinosinusitis

DO Antibiotic duration 5-7 days

Nasal saline irrigation

Intranasal corticosteroids

Consider changing abx if

Clinically worse at 48-72 hours

No improvement at 3-5 days

DO NOT Decongestants

Antihistamines

NP swab

GAS pharyngitis

Accounts for 15% of adult sore throat visits

Dx: culture or rapid antigen test

Tx :

1st line = PCN or amoxicillin x 10 days

Mild PCN allergy = cephalexin x 10 days

Alternatives = clindamycin or clarithromycin x 10 days OR azithromycin x 5 days

Antibiotic allergies: History is key!

Past reaction Source

Timeline: symptoms & meds

Detailed description

Treatment

Concurrent illness

Workup

Other exposure

Current reaction Timeline: symptoms & meds

Labs, histology

Concurrent illness

Algorithm for the use of cephalosporins in patients with reported penicillin allergy

Practical management of antibiotic allergy in adults. McLean-Tooke et al, J ClinPathol 2011;64:192-199

Acute bronchitis

10 million healthcare visits annually

80% of patient prescribed antibiotics

95% of case have a viral etiology

Antibiotics = No clinical benefit plus increased cost, adverse reactions, increased antibiotics resistance

Skin and Soft Tissue Infections

Skin Infection Anatomy

Epidermis

Dermis

Subcut. Fat

Fascia

Muscle

Impetigo

Erysipelas

Cellulitis

Abscess, furuncle, carbuncle

Fasciitis

Pyomyositis

S. pyogenes Resistance in the U.S. 2002-2003

Antimicrobial Agent Percent Resistant*

Penicillin 0.0%

Cefdinir 0.0%

Clindamycin 0.5%

Erythromycin 6.8%

Azithromycin 6.9%

Clarithromycin 6.6%

Levofloxacin 0.05%

*Richter SS. Clinical Infectious Diseases 2005; 41:599–608

S. aureus Susceptibilities from Outpatient Wound Isolates

Antimicrobial Agent Percent Susceptible*

Oxacillin 52.0%

Trimethoprim-Sulfamethoxazole 99.6%

Clindamycin 86.7%

Erythromycin 41.5%

Tetracycline 93.8%

Vancomycin 100%

*http://ww2.cdph.ca.gov/PROGRAMS/MDL/Pages/CaliforniaAntibiogramProject.aspx

Risk Factors for CA-MRSA

Prior history of MRSA infection

Close contact with person with similar infection

Recent antibiotic use

Reported “spider bite”

Outbreaks in IVDU, prisoners, athletes, children, Native Americans

Cellulitis vs Abscess

Cellulitis Abscess Pathogen Beta-hemolytic streptococci Staph aureus (CA-MRSA)

Treatment Antibiotics Incision and Drainage+/- ABX

Antibiotics • Penicillin (amoxicillin)• Cephalosporins (cephalexin)• Clindamycin (PCN allergic)• TMP/SMX???

• TMP/SMX • Doxycycline • Clindamycin • Linezolid $$$

Duration 5-10 days; monitor clinical response

Abscess: when to prescribe abx?

Antibiotics may be warranted if

Abscess is large (> 5 cm) or incompletely drained

Significant surrounding cellulitis

Systemic signs and symptoms of infection are present

Patient is immunocompromised

Difficult to drain area (face, hand, genitalia)

Extremes of age

Animal & Human Bite Wounds

One half of all Americans bitten in their lifetime

80% of wounds are minor, 20% require medical care

Human and cat bites frequently become infected so always require treatment even if not grossly infected

Only 5% of dog bites get infected so treatment indicated if bite is severe, grossly infected, or significant comorbidity (e.g. diabetes)

Bite Wound Treatment

Wound cleaning, irrigation and debridement!

Antibiotics directed against skin flora of patient and oral flora of biting animal/human

Humans (viridans strep, Eikenella, mixed anaerobes)

Dogs (Pasteurella, Capnocytophaga, anaerobes)

Cats (Pasteurella, anaerobes)

Antibiotic Regimens

Oral

Amoxicillin/clavulante 875/125 mg BID

Clindamycin + Fluoroquinolone OR TMP/SMX

IV : Ampicillin/sulbactam 1.5G Q6h

Urinary Tract Infections

Increasing resistance in urinary pathogens

E.coli accounts for ~95% of all cases

TMP/SMX resistance in E.coli > 20% in many parts of the United States

Resultant shift to use of quinolones as first-line empirical therapy over the past 10-20 years

Quinolones have been associated with “collateral damage”

Increased rates of MRSA

Selection for resistant GNRs including ESBL- producers

Clostridium difficile-associated diarrhea

When to get a culture?

Suspect multidrug-resistant organism

Recent abx

Prior infection or colonization

Recent travel

Suspect pyelonephritis

Follow up cultures unnecessary in patients whose symptoms resolve

2010 IDSA recommended treatment regimens for uncomplicated cystitis

First Line Regimens Nitrofurantoin macrocrystals

(Macrobid®) 100 mg BID X 5 days (avoid if early pyelo suspected)

Trimethoprim-sulfamethoxazole 1DS tablet BID X3 days (avoid if resistance prevalence exceeds 20% or if used for a UTI in previous 3 months)

Fosfomycin trometamol 3 grams x 1 dose (lower efficacy than some other agents, avoid if early pyelo suspected)

Second Line Regimens Ciprofloxacin 500 mg BID x 3 days

(resistance prevalence high in some areas)

Oral β-lactams (including amoxicillin/clavulante, cefdinir, cefaclor, cefpodoxime, cephalexin (less data); avoid ampicillin or amoxicillin alone; lower efficacy than other available agents, treat for 3 to 7 days)

Gupta K et al. Clin Infect Dis. 2011;52(5):103-20.

What is fosfomycin? Phosphonic acid derivative that inhibits cell wall synthesis

Activity against many gram positive and gram negative organisms

In U.S., only oral salt available as a powder sachet dissolved in water

High concentration in the urine

Usual dose 3g x 1 (single dose)

Can also consider 3g every other day x 3 doses or 3g q 72 hrs. x 14 days

3g packet costs about $50

Treatment of cystitis: Back to the future

Nitrofurantoin (Macrobid®)

PROS

As effective as TMP/SMX

Minimal drug resistance

Low propensity for collateral damage

CONS

Blood levels not sufficient to treat early pyelonephritis

Avoid in pts with CrCl < 50 ml/min

Nausea, headache (similar adverse effect rate as TMP/SMX)

Rare pulmonary hypersensitivity

Fosfomycin trometamol

PROS

Clinical efficacy similar to TMP/SMX

Low propensity for collateral damage

Single dose therapy

CONS

Microbiologic efficacy lower than TMP/SMX and nitrofurantoin

Not sufficient to treat early pyelo

Susceptibility testing not routinely performed

Diarrhea, nausea, headache (similar adverse effect rate as nitrofurantoin)

Other oral options for cystitis due to resistant organisms

Amoxicillin-clavulanate (susceptible ESBL-producing E. coli)

Nitrofurantoin

Fosfomycin references:

Falagas et al, Lancet Infect Dis 2010;10:43-50

Neuner et al, Antmicro Agents Chemother 2012;56:5744-48

Asymptomatic Bacteriuria

Do not screen if no symptoms are present

Except in pregnancy

Other special situations

Do not prescribe antibiotics!

Relative Risk ~3x for recurrence of symptomatic bacteriuria when asymptomatic patients receive antibiotics

Final Questions?

Contact Info

Extension: 415-206-5574

Email: daniel.deck@sfdph.org

SFGH “As real as it gets”