6/1/2015

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COMMUNITY-ACQUIRED

INFECTIONS

Cyle White, Pharm.D, BCPS

Infectious Diseases Pharmacist

Erlanger Health System

Disclosure Statement

The presenter has nothing to disclose concerning possible

financial or personal relationships with commercial entities

(or their competitors) that may be referenced in this

presentation.

Outline

• Antimicrobial Resistance/Stewardship

• Skin and Soft Tissue Infections (SSTIs)

• Upper Respiratory Tract Infections (URTIs)

• Rhinosinusitis

• Pharyngitis

• Acute bronchitis

• Urinary Tract Infections (UTIs)

• Acute Exacerbation of Chronic Obstructive Pulmonary

Disease (AECOPD)

Centers for Disease Control and Prevention

Public Perception

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Outpatient Antibiotic Use

• The vast majority of all antibiotics for human use are in

the outpatient setting

• Higher levels of outpatient antibiotic use have been linked

to higher rates of resistance

• 0.9 prescriptions per capita, 1.2 in TN, WV, and KY

• Education and intervention with feedback can significantly

decrease prescribing and increase guideline adherence

JAMA. 2013;309(22):2345-2352.

Clin Infect Dis. 2011;53:640-643.

Skin and Soft Tissue Infections

Streptococcal cellulitis

https://www.asdk12.org/staff/johansen_annette/pages/Website%20real%20text/Cellulitis.html

CA-MRSA and “Spider Bites”

CDC 2013. http://www.cdc.gov/mrsa/community/photos/index.html.

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SSTI Agents

• Strep

• Cephalexin (qid)

• Cefadroxil (bid)

• Amoxicillin (tid)

• Penicillin VK (qid)

• Clindamycin

• Linezolid

• MRSA

• TMP/Sulfa

• Doxycycline

• Clindamycin

• Linezolid

MRSA

Drug % Susc

TMP/Sulfa 94

Doxycycline 92

Clindamycin 19

Linezolid 100

Erlanger Antibiogram 2014

CA-MRSA Agents

• Drug Updates:

• Sulfamethoxazole/trimethoprim: 1 DS tabs BID = 2 DS tabs BID

for CA-MRSA SSTI clinical resolution

• Clindamycin:

• D-test should be performed prior to use of clindamycin for CA-MRSA

when cultures can be obtained

• Poor empiric choice based on local susceptibilities

• Oxazolidinones $$$

• Linezolid

• Tedizolid (Sivextro®) 200mg daily x 6 days

Antimicrob Agents Chemother. 2011;55(12):5430-5432.

J Infect Dis. 2001;184(11):1437-1444.

CDC 2010. http://www.cdc.gov/mrsa/treatment/outpatient-management.html .

CA-MRSA Empiric Selection

SSTI diagnosis

Fluctuance, pus, aspirate

Likely CA-MRSA

SMX-TMP, Doxycycline

Non-purulent, diffuse wound

Likely Strep

Cefadroxil, Amoxicillin

CA-MRSA still suspected:

Doxy, clinda

Upper Respiratory Tract Infections (URTIs)

• Rhinosinusitis

• Pharyngitis

• Acute bronchitis

Rhinosinusitis

• Bacterial vs. Viral:

• Persistent symptoms lasting ≥ 10 days (no improvement)

• Severe or worsening symptoms (3-4 days)

• High-grade fever (>102°F)

• Facial pain, headache

• Increase in purulent nasal discharge

• Treatment: 5-7 days adults, 7-10 days children

• Viral: supportive care

• Bacterial: Amoxicillin/clavulanate 2 g po BID

• PCN allergy: Levofloxacin/moxifloxacin, doxycycline

• No longer recommended: Azithromycin, 3rd-gen cephalosporins unless

combined with clindamycin

Clin Infect Dis. 2012;54(8):72-112.

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Pharyngitis

• Viruses most common cause followed by GABHS

• Testing: bacterial vs. viral

• Rapid antigen detection test (RADT) for GAS

• High suspicion even with negative RADT in the presence of patchy

tonsillopharyngeal exudates, cervical adenopathy, fever, esp. age

5-15 years

• Not needed for patients with suspected viral infection:

• Cough, rhinorrhea, hoarseness, oral ulcers

• Treatment for diagnosis of GAS Pharyngitis: 10 days

• PCN/amoxicillin

• PCN allergy: cephalexin/cefadroxil, clindamycin, azithromycin

Clin Infect Dis. 2012;55(10):e86-e102.

Acute Bronchitis

• Mostly viral

• 60-90% of patients receive antibiotics

• Cough usually lasts for 10-20 days

• Reassurance to patients

• Antibiotics ineffective

• Side effects and resistance

Prim Care Respir J. 2010;19(3):237.

Ann Intern Med. 2001;134(6):518.

Urinary Tract Infections

Cystitis

vs

Pyelonephritis

Diagnosis

• Symptoms

• Dysuria, frequency, urgency, suprapubic pain

• Pyelonephritis- CVA tenderness, fever, N/V

• Urinalysis

• Leukocyte Esterase

• WBC >10/HPF

• Nitrites

• Epis <5/HPF

Complicated vs Uncomplicated Cystitis

• Complicated

• Urologic abnormalities (e.g. neurogenic bladder, stone, stents, indwelling catheter)

• Pregnancy

• Immunocompromised

• Preadolescent

• Postmenopausal

• Diabetes mellitus

• Male gender

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E. coli

Drug % Susc

Nitrofurantoin 97

Cephalexin 87

TMP/Sulfa 67

Levofloxacin 61

Ciprofloxacin 58

Erlanger Antibiogram 2014

Treatment: Uncomplicated Cystitis

Clinical Infectious Diseases 2011;52(5):e103–e120.

Agent Dose Duration

Fosfomycin

(Monurol®)

3g packet 1 day

Trimethoprim/sulf

amethoxazole

(TMP/SMX)

1 DS tab BID

3 days Alternative:

Ciprofloxacin

Levofloxacin

250mg BID

250mg daily

Nitrofurantoin

(Macrobid®)

100mg BID

5 days Alternative:

Cephalexin

Cefadroxil

Cefuroxime

Cefpodoxime

500mg BID

1g daily or BID

250mg BID

100mg BID

Treatment: Complicated Cystitis

Clinical Infectious Diseases 2011;52(5):e103–e120.

Pharmacotherapy. 2014 Aug;34(8):845-57.

Agent Dose Duration

Cephalexin

Cefadroxil

Cefuroxime

Cefpodoxime

TMP/SMX

500mg BID

1g daily or BID

250mg BID

100mg BID

1 DS tab BID

7-10 days

Nitrofurantoin

(Macrobid®) 100mg BID 7 days

Levofloxacin 750mg daily 5 days

Ciprofloxacin 500mg BID 5-7 days

Fosfomycin

(Monurol®) 3g q48h 3 doses

Treatment: Pyelonephritis

Clinical Infectious Diseases 2011;52(5):e103–e120.

Agent Dose Duration

Cefuroxime

Cefpodoxime

Cefixime

TMP/SMX

500mg BID

200mg BID

400mg daily

1 DS tab BID

10-14 days

Levofloxacin 750mg daily 5 days

Ciprofloxacin 500mg BID 7 days

Antimicrobial Agents

Advantages Disadvantages

Nitrofurantoin Low resistance, low collateral damage

Ineffective CrCL <40 AE- rare neuropathy, pulmonary fibrosis

Trimethoprim/ sulfamethoxazole

Low collateral damage, low cost

2C9 inhibitor AE- rash, hematologic disturbances, allergies, AKI, hyperkalemia

Fosfomycin Single dose, low collateral damage

Lower efficacy

Antimicrobial Agents

Advantages Disadvantages

Ciprofloxacin High efficacy (when susceptible), reserve for more serious infections

Increasing resistance, broad coverage, high collateral damage, drug interactions AE- CNS, dysglycemia, tendonopathy, QT prolongation

Levofloxacin

Penicillins (Amoxicillin, etc) Lower collateral damage, DOC for Enterococcus

Lower efficacy, high resistance

Cephalosporins Low E. coli resistance High collateral damage, Enterococcus intrinsically resistant

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Pregnancy

• Increased likelihood to develop UTI from asymptomatic

bacteriuria

• Asymptomatic: 3-7 days Symptomatic: 5-10 days

• Agents in pregnancy

– Amoxicillin +/- clavulanate

– Cephalexin

– Nitrofurantoin (Avoid in 3rd trimester)

– TMP/SMX (Avoid in 3rd trimester)

Urol Clin North Am 2007;34(1):35–42.

Recurrent

• ≥ 2 symptomatic UTIs in 6 mo or ≥3 in 12 mo

• Antimicrobial Prophylaxis

• Nitrofurantoin: 50-100 mg

• TMP-SMX: ½ SS tab (3x weekly also effective)

• TMP: 100 mg

• Cephalexin: 125-250 mg

• Fosfomycin: 3g packet every 10 days

N Engl J Med 2012;366:1028-37.

Acute Exacerbation of Chronic

Obstructive Pulmonary Disease

(AECOPD)

COPD Prevalence

MMWR. 61(46);938-943.

Int J Chron Obstruct Pulmon Dis. 2008;3(1):31-44. Med Clin N Am 96:4(2012).

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Antibiotic Use

• Use of antimicrobials in exacerbations

remains controversial

• GOLD guidelines: antimicrobial selection

based on local susceptibilities

• “Collateral damage” of antimicrobial use

Global Strategy for the Diagnosis, Management and Prevention of COPD, Global

Initiative for Chronic Obstructive Lung Disease (GOLD) 2015.

Curr Opin Microbiol. 2000; 3:496–501.

Antibiotics in COPD:

When and which ones?

GOLD Guidelines Recommendation

• Antibiotics should be given in patients with:

• 3 cardinal symptoms of increased dyspnea, sputum volume, sputum purulence (evidence B)

• 2 of 3 cardinal symptoms (evidence C)

• Choice of antibiotic based on local susceptibilities

Cochrane review

The Cochrane Library 2012, Issue 12

Antibiotic Comparison Trials

• Older studies: mostly no difference between

agents

• Newer studies:

• GLOBE

• MOSAIC

• MAESTRAL

Fluoroquinolone risks

• Tendonopathy

• Dysglycemia

• Neuropathy

• Musculoskeletal

• Acute kidney injury

• QT prolongation

• Decreased barrier for resistance

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Risk Stratification

3 Cardinal Symptoms

• Increased dyspnea

• Increased sputum volume

• Increased sputum purulence

Sputum Color

Respir Med. 2005 Jun;99(6):742-7. Clin Microbiol Infect 2010; 16: 583-588.

Patient stratification

• Risks for poor outcomes

• Increasing age

• Underlying severity of lung dysfunction

• Co-morbid illnesses

• History of recurrent exacerbations

• Chronic oral steroid therapy

• Chronic home O2 therapy

• Hypercapnia

• Signs of infection

Choice and Duration

• Antibiotic: based on local susceptibilities

• Amox/clav

• Cefdinir

• TMP/SMX

• Doxycycline

• Levofloxacin

• Moxifloxacin

• 3-10 days

• 5d as effective as >7 with less side effects

Global Strategy for the Diagnosis, Management and Prevention of COPD, Global

Initiative for Chronic Obstructive Lung Disease (GOLD) 2015.

J Antimicrob Chemother. 2008;62(3):442.

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Summary

• Antibiotic resistance

• SSTI

• Staph vs strep

• URTI

• Most receive antibiotics, few should

• UTI

• Higher resistance to FQs

• AECOPD

• Risk stratify 5 days

COMMUNITY-ACQUIRED

INFECTIONS

Cyle White, Pharm.D, BCPS

Infectious Diseases Pharmacist

Erlanger Health System

cylewhite@gmail.com