Antibiotic Choices

Gary Skankey, MD, FACP

Outline

When to use and when not to use

antibiotics
Interpreting cultures
Choosing appropriate empiric
antibiotics
Using antibiograms

Appropriate Use of Antibiotics

Employ empirically when there is a reasonable

clinical suspicion of infection
Choose antibiotics active against the most likely
organism(s)
Choose antibiotics known to penetrate involved
tissue
Use correct doses of antibiotics dont underdose
Know when bacterostatic antibiotics are adaquate
or bacterocidal drugs are required
In serious, potentially life-threatening infections,
start broad, then de-escalate after cultures back
Stop antibiotics when infection resolved or when
evidence accumulates against existence of
infection

Inappropriate Uses of Antibiotics

Using wrong antibiotic for apparent infection

Using wrong dose of right drug
Using a 2nd or 3rd line drug when a first line drug
could still be used
Using antibiotics in situations when antibiotics are
not indicated just in case
Continuing antibiotics when infection is resolved
or not likely
Keeping coverage broad when cultures reveal a
single organism
Reacting to culture results by starting antibiotics
without considering the significance of the culture

Results of Antibiotic Misuse

Incomplete, delayed, or failed

resolution of infection
Prolonged or unnecessary
hospitalizations
Increased incidence of antibiotic side
effects
Development of multi-drug resistant
strains of bacteria
Increased cost of health care

Knowing When and When Not to Use

an Antibiotic

Infection is Diagnosed Clinically

Based on Multiple Data Points

Pneumonia
Fever
Leukocytosis
Purulent sputum
New infiltrate
Cough, chest pain, dyspnea
Hypoxia
Sputum gram stain shows many WBCs,
few epithelial cells

Infection is Diagnosed Clinically

Based on Multiple Data Points

UTI
Dysuria
Urinary frequency
Fever
Pelvic or flank pain
Pyuria

Watch the number of epithelial cells in U/A

Infection is Diagnosed Clinically

Based on Multiple Data Points

Wound infection
Wound is foul smelling
Skin surrounding wound is red,
indurated, tender
Pus draining from wound
Fever
leukocytosis

Infection is Diagnosed Clinically

Based on Multiple Data Points

Infections are not diagnosed by

culture alone

Mistakes Doctors Make in

Diagnosing Infection

Base their diagnosis on a single positive

data point when other data points are
negative
React to a positive culture when there is
no clinical evidence of infection
Use serial cultures to determine when
infection has resolved
Obtain cultures randomly when clinical
suspicion of infection is low

Interpreting cultures

First Step: Determine Whether

Culture Represents Real Pathogen

Colonizer
And organism actually present in or on
patient, but does not invade tissue or
cause clinical disease

Contaminant
And organism growing in culture that is
not actually present in or on the patient,
but came from the environment directly
to the culture medium

First Step: Determine Whether

Culture Represents Real Pathogen

Every positive culture needs to be

interpreted with respect to other
data points
Example:
A wound culture taken from a cleanappearing, granulating wound that is
not painful, has no purulence in a
patient with no fever and a normal WBC
is a colonizer and should not be treated

First Step: Determine Whether

Culture Represents Real Pathogen

Example:
A sputum culture taken from a patient
without fever, leukocytosis, new
infiltrate or pulmonary symptoms is a
colonizer

Example:
A urine culture taken from a patient
without dysuria, frequency, and with a
small to moderate amount of WBC in
the U/A has asymptomatic bacteriuria

Interpreting Individual Cultures

Blood Cultures

Pathogen if:
Patient is febrile when
culture drawn
Fever persists without
appropriate antibiotics
Organism is a known
pathogen
Grows in 2 of 2 sets
Grows in 24 to 48
hours

Contaminant if:
Patient is afebrile
when culture drawn
No fever despite lack
of appropriate
antibiotic
Organism is a skin
colonizer
Grows in only one set
Grows after 48 hours
Note: Increased risk
of contamination if
drawn through line

Sputum Cultures

A pathogen if:
Sputum is grossly
purulent
Patient is febrile
Infiltrates on CXR
> 5-10 WBC per
hpf
< 5-10 epithelial
cells per hpf

A colonizer if:
Sputum is scant,
clear or white
Patient is afebrile
No infiltrates on
CXR
< 5-10 WBC per
hpf
> 5-10 epithelial
cells per hpf

Urine Cultures

A pathogen if:
> 100,000 cfu
If urinalysis
reveals:

> 10 WBC
Pos. leuk. esterase
Pos. nitrite
Few or no epis

If patient
symptomatic

A contaminant if:
10,000 cfu or less
If urinalysis
reveals:

< 10 WBC
Neg. leuk. esterase
Neg. nitrite
Many epis

If patient
asymptomatic

Asymptomatic bacteriuria

> 100,000 cfu bacteria in urine

culture in a patient with no
symptoms
Incidence increases in women by 1%
per decade
70 80 year olds have 7 8% annual
incidence

Prevalence in elderly
Men 10%
Women 20%
In nursing homes, prevalence is higher

Asymptomatic bacteriuria

NO increased morbidity or mortality

if left untreated
Spontaneously resolves
If treated, patient subjected to
potential side effects of antibiotics
and selective pressure for MDR
organisms unnecessarily
Dont culture urine if no symptoms

Choosing the Right Empiric Antibiotic

Antibiotics for Head and Neck

Infections

Organisms
Streptococcus viridans group, Lancefield group
streptococci, staphylococcus,
peptostrepococcus, Veillonella, fusobacterium,
bacteroides spp, eikonella, etc.

Antibiotics

Beta lactam/beta lactamase inhibitor combos

Clindamycin
2nd generation cephalosporins
4th generation Quinolones (moxifloxacin)

Antibiotics for Meningitis

Organisms
Most common - Streptococcus pneumoniae,
Neisseria meningitidis
Less common (in very young, elderly, or
immunecompromised) Haemophilus
influenzae, Klebsiella pneumoniae, Listeria
monocytogenes

Antibiotics
High dose ceftriaxone, cefotaxime, and
vancomycin (+ ampicillin)

Antibiotics for Community-Acquired

Pneumonia (CAP)

Organisms:
S. pneumoniae, H. influenzae, M.
catarhalis, K. pneumoniae, M.
pneumoniae, C. pneumoniae, L.
pneumophila

Antibiotics
2nd or 3rd generation cephalosporins
Respiratory quinolones (Levofloxacin,
Gatifloxacin)
Advanced macrolides (clarithromycin,
azithromycin)

IDSA Guidelines for Empiric

Treatment of Outpatient CAP

Previously healthy, no use of abx in past 3

months
A macrolide (Biaxin, Azithromycin)
Doxycycline

Comorbidities, immune suppression, abx

in last 3 months

Respiratory FQ (Avelox, Tequin, Levaquin [750

mg])
Beta-lactam (cefuroxime, amox/clav) plus
macrolide (clarithromycin, azithromycin)

If high incidence of macrolide-resistant

pneumococcus, substitute FQ for
macrolide

IDSA Guidelines for empiric

treatment of Inpatient CAP

Non-ICU
Respiratory FQ
Beta-lactam (ceftriaxone, amp/sulb) or
ertapenem plus macrolide

ICU
Beta-lactam or ertapenem plus
macrolide or resp FQ
(I add vancomycin to cover
cephalosporin-resistant pneumococcus
or CA-MRSA)

Timing and duration of therapy for

CAP

First dose must be given in ER

Outcome dependent on early institution
of appropriate antibiotics

Switch from IV to PO abx when pt

hemodynamically stable and
improving clinically, is able to ingest
medications, and has a normally
functioning gastrointestinal tract

Timing and duration of therapy for

CAP

Rx for a minimum of 5 days, should be

afebrile for 4872 h, and should have no
more than 1 CAP-associated sign of
clinical instability before discontinuation of
therapy
Criteria for clinical stability
1) Temperature 37.8C, 2) Heart rate 100
beats/min, 3) Respiratory rate 24 breaths/min,
4) Systolic blood pressure 90 mm Hg, 5)
Arterial oxygen saturation 90% or pO2 60
mm Hg on room air, 6) Ability to maintain oral
intake, 7) Normal mental status

Healthcare Associated Pneumonia

(HCAP)

HCAP

Healthcare associated pneumonia (HCAP)

Any hospitalization in the past 90 days
Any IV antibiotics in the past 30 days
Resident of or transferred from a long term
acute care facility or skilled nursing facility

Likely to be due to MDR hospital-acquired

organisms
Pseudomonas, MDR acinetobacter, ESBL
Klebsiella, MDR enterobacter, etc
MRSA

These patients are too frequently started

on standard CAP empiric antibiotics

Empiric Therapy for HAP, VAP and HCAP in

Patients With Late-onset Disease or Risk Factors for
MDR Pathogens and all Disease Severity
Potential Pathogens
MDR pathogens
P aeruginosa
K pneumoniae
(ESBL+)
Enterobacter
Acinetobacter sp

MRSA

Combination Therapy
Antipseudomonal cephalosporin
(cefepime, ceftazidime)
or
Antipseudomonal carbepenem
(imipenem or meropenem) or
Beta-lactam/beta-lactamase inhibitor
(piperacillin-tazobactam)
plus
Antipseudomonal fluoroquinolone*
(ciprofloxacin or levofloxacin)
or
Aminoglycoside
(amikacin, gent, tobra)
plus

Linezolid
vancomycin
*If an ESBL+ strain (eg, K pneumoniae or an Acinetobacter
sp) is or
suspected,
a carbepenem is a reliable choice. If L
pneumophila is suspected, the combination regimen should include a macrolide (eg, azithromycin) or a
fluoroquinolone (eg, ciprofloxacin or levofloxacin) rather than an aminoglycoside. If MRSA risk factors are present, or
there is a high incidence locally.

ATS. Am J Respir Crit Care Med. 2005;171:388-416.

Antibiotics for Intra-abdominal

Infections

Organisms
Enteric gram negatives, gram negative
anaerobes, gram positive anaerobes,
oral anaerobes, yeast

Antibiotics
Zosyn, Unasyn, Primaxin, Meropenem
Ceftriaxone or Cefotaxime + Flagyl +
Vancomycin
+ Fluconazole

Antibiotics for Urinary Tract Infections

Organisms
Gram negative enterics, enterococcus

Antibiotics
Ciprofloxacin, Levafloxacin, 2nd or 3rd
generation cephalosporins,
amoxacillin/ampicillin (if sensitive)

Antibiotics for Skin and Soft Tissue

Infections

Organisms
Staphylococcus (75% MRSA),
streptococcus

Antibiotics
PO TMP/SMX, Clindamycin, Linezolid
IV Vancomycin, Daptomycin

Antibiogram HA-MRSA vs CA-MRSA

HA-MRSA
Sensitive to:

Vancomycin
TMP/SMX
Rifampin

Resistant to:

Oxacillin
Cephalosporins
Quinolones
Tetracyclines
Erythromycin
clindamycin

CA-MRSA
Sensitive to:

Vancomycin
TMP/SMX
Rifampin
Tetracyclines
Erythromycin
Clindamycin
Quinolones

Resistant to:

Oxacillin
Cephalosporins

Antibiotic Resistance

Things that promote drug

resistance

Using antibiotics when no infection is present

The just-in-case syndrome

Treating cultures, not patients

Colonizations or contaminants

Using the incorrect empiric antibiotic

Example: using Levaquin for cellulitis

Continuing antibiotics past the point that infection has

resolved
Failing to de-escalate antibiotic coverage after cultures are
finalized
Underdosing antibiotics
Using an antibiotic that does not penetrate to the focus of
infection
Example: using doxycycline for UTI

Using a bacterostatic antibiotic when an infection calls for

bacterocidal action

Spread of MDR Organisms

Study at Johns Hopkins Medical

Center
Only 40% of HCWs wash hands
regularly and appropriately between
every patient
Of HCWs doctors were the worst
washing hands only 18% of the time

MDRs are also transmitted on

medical instruments
stethoscopes

Cultured-Based Antibiotic Choice

Know Your Local Antibiograms

Sensitivities of community-acquired
and hospital-acquired organisms
vary from region to region
Knowledge of the general
sensitivities will aid in choosing
appropriate antibiotics and early
institution of therapy

Inappropriate Antibiotic Therapy

Increases Mortality
Appropriate therapy

Inappropriate therapy

Mortality (%)

100
90
80
70
60
50
40
30
20
10
0
Ibrahim

Leibovici

Bloodstream Infections

Luna

Alvarez-Lerma

Rello

Nosocomial Pneumonia/VAP

Ibrahim, et al. Chest. 2000;118:146155.

Leibovici, et al. J Intern Med. 1998;244:379386.
Luna, et al. Chest. 1997;111:676685.
Alvarez-Lerma, et al. Intensive Care Med.1996;22:387394.
Rello, et al. AJRCCM.1997;156:196200.

Hospital Mortality Rate of

Infected Patients

2000 consecutive patients

admitted to an MICU or
SICU
Pneumonia in 411 cases

Mortality %

60
50
40

30
305 with adequate therapy
106 with inadequate therapy 20

52.1%

N = 312
P<.001

12.2%

10
0

Inadequate Adequate
Antibiotic Treatment

Kollef, et al. Chest. 1999;115:462474.

Interpreting in vitro Sensitivity

MIC minimum inhibitory concentration

In order to adequately kill bacteria, serum
concentration must be at least 8x the MIC
Sensitivity break-points vary among
different antibiotics, because of
differences in pharmacodynamics
Best drugs to use are those with lowest
MIC

Interpreting in vitro Sensitivity

Panels

Not every antibiotic listed as sensitive in

vitro will be effective in vivo
Must consider tissue penetration
Ancef does not penetrate CSF
Tetracycline is not excreted in urine

Must consider killing power

Clindamycin is too slowly bacterocidal to be
useful in treating bacteremia
Any bacterostatic antibiotic is contraindicated
in treating serious infections like endocarditis
and meningitis

Antibiograms

Sensitivity to Hospital-Acquired
Gram Negatives City Wide
100
90
80
70
60

Meropenem
Cefepime
Pip/Tazo
Levaquin

50
40
30
20
10
0
Pseudo

E. cloacae

Acinetob

K. pneumo

Sensitivity to Gram Positives City

Wide
100
90
80
70
60

Ceftriaxone
Vancomycin
Penicillin
Linezolid

50
40
30
20
10
0
S.aureus

S.pneumo

E.faecium

Hospital-Specific Antibiogram
100
90
80
70
60

Meropenem
Cefepime
Pip/Tazo
Cipro

50
40
30
20
10
0
Pseudo-City

Pseudo-UMC

Hospital-Specific Antibiogram
100
90
80
70
60

Oxacillin
Vancomycin
Clindamycin
Levaquin

50
40
30
20
10
0
S.aureus-City

S.aureus-UMC

Summary

Use antibiotics judiciously to

minimize treatment failure, higher
morbidity and mortality and reduce
development of resistance
Know the antibiograms of you
respective hospitals to guide choice
of antibiotics
Thoroughly evaluate every patient so
that correct diagnosis is made