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 – don’t 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 clean-
appearing, 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: „ A colonizer if:
„ Sputum is grossly „ Sputum is scant,
purulent clear or white
„ Patient is febrile „ Patient is afebrile
„ Infiltrates on CXR „ No infiltrates on
„ > 5-10 WBC per CXR
hpf „ < 5-10 WBC per
„ < 5-10 epithelial hpf
cells per hpf „ > 5-10 epithelial
cells per hpf
 Urine Cultures
„ A pathogen if: „ A contaminant if:
„ > 100,000 cfu „ 10,000 cfu or less
„ If urinalysis „ If urinalysis
reveals: reveals:
• > 10 WBC • < 10 WBC
• Pos. leuk. esterase • Neg. leuk. esterase
• Pos. nitrite • Neg. nitrite
• Few or no epi’s • Many epi’s
„ If patient „ If patient
symptomatic 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
„ Don’t 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 48–72 h, and should have no
more than 1 CAP-associated sign of
clinical instability before discontinuation of
therapy
„ Criteria for clinical stability
• 1) Temperature 37.8°C, 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 Combination Therapy
MDR pathogens Antipseudomonal cephalosporin
• P aeruginosa (cefepime, ceftazidime) or
• K pneumoniae Antipseudomonal carbepenem
(ESBL+) (imipenem or meropenem) or
• Enterobacter Beta-lactam/beta-lactamase inhibitor
• Acinetobacter sp (piperacillin-tazobactam)
plus
Antipseudomonal fluoroquinolone*
(ciprofloxacin or levofloxacin)
or
Aminoglycoside
(amikacin, gent, tobra)
• MRSA plus

Linezolid
*If an ESBL+ strain (eg, K pneumoniae or an Acinetobacter sp) is or vancomycin
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 „ CA-MRSA
• Sensitive to: • Sensitive to:
„ Vancomycin „ Vancomycin
„ TMP/SMX „ TMP/SMX
„ Rifampin „ Rifampin
• Resistant to: „ Tetracyclines
„ Oxacillin „ Erythromycin
„ Cephalosporins „ Clindamycin
„ Quinolones „ Quinolones
„ Tetracyclines • Resistant to:
„ Erythromycin „ Oxacillin
„ clindamycin „ 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
100
90
80
Mortality (%)

70
60
50
40
30
20
10
0
Ibrahim Leibovici Luna Alvarez-Lerma Rello
Bloodstream Infections Nosocomial Pneumonia/VAP

Ibrahim, et al. Chest. 2000;118:146–155.

Leibovici, et al. J Intern Med. 1998;244:379–386.
Luna, et al. Chest. 1997;111:676–685.
Alvarez-Lerma, et al. Intensive Care Med.1996;22:387–394.
Rello, et al. AJRCCM.1997;156:196–200.
 Hospital Mortality Rate of
Infected Patients

„ 2000 consecutive patients 60 52.1%

admitted to an MICU or 50
SICU N = 312

Mortality %
P<.001
„ Pneumonia in 411 cases 40

• 305 with adequate therapy 30

• 106 with inadequate therapy 20 12.2%

10

0
Inadequate Adequate

Antibiotic Treatment

Kollef, et al. Chest. 1999;115:462–474.

 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
50 Cefepime
40 Pip/Tazo
30 Levaquin
20
10
0
Pseudo E. cloacae Acinetob K. pneumo
Sensitivity to Gram Positives – City
Wide
100
90
80
70
60 Ceftriaxone
50 Vancomycin
40 Penicillin
30 Linezolid
20
10
0
S.aureus S.pneumo E.faecium
Hospital-Specific Antibiogram
100
90
80
70
60 Meropenem
50 Cefepime
40 Pip/Tazo
30 Cipro
20
10
0
Pseudo-City Pseudo-UMC
Hospital-Specific Antibiogram
100
90
80
70
60 Oxacillin
50 Vancomycin
40 Clindamycin
30 Levaquin
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