In the Clinic: Evidence Based Management of Infections Daniel Deck, Pharm.D.

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
Fever or hypothermia
Cough
Rigors and/or diaphoresis
Chest pain
Sputum production or color change
Dyspnea
New infiltrate on chest x-ray and/or
abnormal chest exam
No hospitalization or other nursing
facility prior to symptom onset
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 culture
 Remains 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%
 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%
“Atypicals”
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 age
Alcoholism
COPD and/or smoking
Nursing home residence
Influenza
Injection drug use
Airway obstruction
*HIV infection
S. pneumoniae – drug resistance



~ 25-35% penicillin non-susceptible by old
standard nationwide, but most < 2 mg/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 nonsusceptible


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

CHF

Alcoholism

CAD

Leukopenia

Malignancy

Bacteremia

Neurologic disease

Diabetes mellitus

Chronic liver disease

Renal insufficiency

Immunosuppression
IDSA Outpatient Empiric Therapy
Recommendations
Previously Healthy & NO
DRSP Risk Factors
DRSP Risk Factors or High Level
Macrolide Resistance > 25%
Macrolide (e.g azithromycin)
or
Doxycycline
1) Fluoroquinolone* or
2) a β-Lactam# plus
a Macrolide or Doxycycline
*moxifloxacin, gemifloxacin, or levofloxacin (750mg)
1 gm PO tid or Augmentin® XR 2 gm PO bid are preferred. Ceftriaxone,
cefpodoxime proxetil, and cefuroxime axetil 500 mg PO bid are alternatives
#Amoxicillin
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
Minor Criteria

Purulent anterior nasal discharge

Headache

Purulent posterior nasal discharge

Ear pain, pressure, or fullness

Nasal congestion or obstruction

Halitosis

Facial congestion or fullness

Dental pain

Facial pain or pressure

Cough

Hyposomia or anosmia

Fever (chronic disease)

Fever (acute 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
st line therapy =
 1
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
DO NOT
 Decongestants

Nasal saline irrigation

Antihistamines

Intranasal corticosteroids

NP swab

Consider changing abx if
 Clinically worse at 48-72 hours
 No improvement at 3-5 days
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
Current reaction
 Timeline: symptoms & meds

Timeline: symptoms & meds

Labs, histology

Detailed description

Concurrent illness

Treatment

Concurrent illness

Workup

Other exposure
Algorithm for the use of cephalosporins in patients with
reported penicillin allergy
Practical management of antibiotic allergy in adults. McLean-Tooke et al, J Clin
Pathol 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
Impetigo
Erysipelas
Dermis
Subcut. Fat
Fascia
Muscle
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
*Richter SS. Clinical Infectious Diseases 2005; 41:599–608
0.05%
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
Duration
•
•
•
•
Penicillin (amoxicillin)
Cephalosporins (cephalexin)
Clindamycin (PCN allergic)
TMP/SMX???
5-10 days; monitor clinical
response
•
•
•
•
TMP/SMX
Doxycycline
Clindamycin
Linezolid $$$
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
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)
Gupta K et al. Clin Infect Dis. 2011;52(5):103-20.
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)
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
Fosfomycin trometamol
PROS

As effective as TMP/SMX

Clinical efficacy similar to TMP/SMX

Minimal drug resistance

Low propensity for collateral damage

Low propensity for collateral damage

Single dose therapy
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
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: [email protected]
SFGH “As real as it gets”