Transcript Symposium3_1

Case Discussion
Objective: Antibiotic usages in ambulatory
medicine
Topics
1. General Principles of Antibiotic Usages
2. Case Discussion
3. Conclusion
Antibiotic Usages in Ambulatory
Cares
• Infecting Organism and Antimicrobial
Susceptibility
• Host Factors:
–
–
–
–
–
–
Hx of adverse drug reaction
Age
Genetic or metabolic abnormalities
Pregnancy
Renal and hepatic function
Site of infection
Antibiotic Usages in Ambulatory
Cares
Antimicrobial Combinations
• Indication for the Clinical Use of
Antimicrobial Combinations
– Prevention of the emergence of resistant
organisms
– Polymicrobial infections
– Initial therapy
– Decrease toxicity
– Synergism
In Vitro Results of Antimicrobial
Combinations
Empirical Indications for Aminoglycosides
Type of Infection
Example (s)
Initial Use in
Combination
with Other
Antimicrobials
Bacteremia, possible
Fever without obvious source
Yes
Burn wound
Burn wound infection
Yes
Endocarditis, infective Streptococcal, enterococcal,
staphylococcal
Yes
Intra-abdominal
Appendicitis, diverticulitis,
cholecystitis, peritonitis
Yes
Meningitis
Post-trauma, postoperative
Yes
Neutropenia and fever Post-chemotherapy
Yes
Ocular
Yes
Endophthalmitis
Empirical Indications for Aminoglycosides
Initial Use in
Combination
with Other
Antimicrobials
Type of Infection
Example (s)
Osteomyelitis/septic
arthritis
Post operative or post-trauma
Yes
Otitis
Malignant external otitis in a
diabetic
Yes
Pneumonia
Respirator-associated
pneumonia
Yes
Pyelonephritis
Patients with chronic Foley
catheter infection
Yes
Sexually transmitted
disease
Pelvic inflammatory disease
Yes
Skin-subcutaneous
tissue
Infected diabetic foot
Yes
Vitro Synergism of an Aminoglycoside Combined
with a Cell Wall-Active Antimicrobial
Organism
Aminoglycosides
Cell Wall-Active Drugs
Enterococci
Streptomycin,
kanamycin,
gentamicin,
tobramycin, netilmicin,
sisomicin, amikacin
Penicillin, ampicillin,
carbenicillin, nafcillin,
vancomycin
S. viridans
Streptomycin
Penicillin
S. pyogenes
Gentamicin
Penicillin, ampicillin
S. aureus, MSSA Kanamycin,
gentamicin,
tobramycin, netilmicin,
sisomicin
Nafcillin, oxacillin,
cephalothin, vancomycin
S. aureus, MRSA Gentamicin,
S. epidermidis,
tobramycin
MSSE, MRSE
Teicoplanin (+ rifampicin)
Vancomycin (+ rifampicin
In Vitro Activity of Trimethoprim against
Representative Organisms
Range of MIC (ug/ml)
Organism
alone
With SMX
0.15 -2
0.04 – 1.6
Staphylococcus epidermidis
0.02
-
Streptococcus pneumoniae
0.004 - 5
0.05 – 1.5
Streptococcus pyogenes
0.02 - 1
0.015 – 0.4
Enterococcus faecalis
0.15 – 0.5
0.015 – 0.4
Corynebacterium diphtheriae
0.15 – 0.5
0.05 – 0.15
Listeria monocytogenes
0.05 – 1.5
0.015 – 0.15
Clostridium perfringens
2 - 50
-
Propionibacterium acnes
0.07
-
Gram – positive organisms
Staphylococcus aureus
In Vitro Activity of Trimethoprim against
Representative Organisms
Range of MIC (ug/ml)
Organism
alone
With SMX
Escherichia coli
0.01 - > 5
0.005 - > 5
Klebsiella spp.
0.15 - 5
0.05 – 3.1
0.15 – 1.5
0.05 – 0.15
0.8 - 50
0.4 - 50
Salmonella spp.
0.01 – 0.4
0.05 – 0.15
Shigella spp.
0.4 – 0.8
0.02 – 0.5
Citrobacter freundii
0.2
-
Vibrio cholerae
0.2
-
0.1 – 12.5
0.004 - 50
Gram–negative organisms
Proteus mirabilis
Serratia marcescens
Haemophilus influenzae
In Vitro Activity of Trimethoprim against
Representative Organisms
Range of MIC (ug/ml)
Organism
alone
With SMX
Neisseria gonorrhoeae
0.2 - 128
0.15 – 3.1
Neisseria meningitidis
3.1 -50
0.01 – 1.6
50 - 1000
3.1 - 100
1-2
-
Stenotrophomonas maltophilia
1 - > 32
1 - > 32
Bacteroides fragilis
> = 4.0
-
3 - 100
1.5
20
-
Gram – negative organisms
Pseudomonas aeruginosa
Burkholderia cepacia
Other organisms
Chlamydia trachomatis
Nocardia asteroides
Antibiotic Usages in Ambulatory
Cares
Antimicrobial Combinations
• Disadvantages of the Inappropriate Use
of Antimicrobial Combinations
– Antagonism
– Cost
– Adverse effects
Antibiotic Usages in Ambulatory
Cares
Choice of Appropriate Route of
Administration and Evaluation of
Efficacy
• Route of Administration
• Monitoring the Response of the Patient
to Antimicrobial Therapy
– SIT, SBT, blood level
– Clinical assessment and vital signs
Pharmacokinetics
And
Pharmacodynamics
Of
Anti-infective Agents
Overview of Interaction of
Pharmacokinetics and Pharmacodynamics
Serum Concentration Versus Time
Profile of Two-Phase
Pharmacokinetics
Definitions and Abbreviations
• Absorptions: F (bioavailability), Ka (absorption
rate constant)
• Distribution: Vd (volume of distribution), Vss
(volume of distribution at steady state)
• Metabolism: Vm (maximum metabolic capacity,
Michaelis-Menten metabolism), Km (drug
concentration at which the rate the an enzyme
system can metabolize the drug is one half of
Vm, CYP (Cytochrome P-450 enzyme systems)
Pharmacokinetics
Definitions and Abbreviations
• Elimination: CLr (renal clearance), CLnr
(non-renal clearance), T1/2 (half-life)
Pharmacodynamics
Definitions and Abbreviations
• MIC90 (minimal inhibitory
concentration for 90% of isolates)
• EC50 (effective concentration for
50% of all isolates)
• IC50 (Inhibitory concentration for
50% of isolates)
Pharmacodynamics
Definitions and Abbreviations
• Cmax/MIC (Ratio of peak antimicrobial
serum concentration to MIC,
concentration-dependent killers)
Pharmacokinetic and MIC
Pharmacodynamic Relationship
Time Kill Curves of P. aeruginosa
Probability Graph of Cmax/MIC Ratio for
Temperature Normalization by Aminoglycoside
in Gram-Negative Pneumonia
Pharmacodynamics
Definitions and Abbreviations
• AUC/MIC (Ratio of 24-hour area under
the blood antimicrobial concentration
versus time curve to (above) MIC ratio
Relationship of AUC/MIC and Clinical (A) or
Microbiologic (B) Cure in Gram Negative
Pneumonia Treated by Ciprofloxacin
Pharmacodynamics
Definitions and Abbreviations
• T > MIC (Time that the blood
antimicrobial concentration is higher than
the organism’s MIC, time-dependent
killers)
• SBT (Serum bactericidal titer,
concentration)
• PAE (Post-antibiotic effect)
The Relationship of Time Above MIC and the
Reduction in Bacterial Count in a Neutropenic
Mouse Model of K. pneumoniae for Cefotaxime
Post Antibiotic Effects
• PAE: a delay before microorganisms recover
and reenter a log-growth period.
• PAE exists against gram-negative organisms for
aminoglycosides, fluoroquinolones,
erythromycin, clindamycin, and tetracycline.
• Beta-lactam agents do produce abbreviated
PAEs against gram-positive organisms.
CASE 1
• This 22 year-old woman developed
an abscess in a cervical lymph node
following severe pharyngitis. What
does the Gram stain of the fluid from
this abscess show?
Gram stain of aspirated fluid from lymph node
Culture of the Aspirated Fluid from the Lymph Node
Test for Production of Catalase
Approach to Acute Pharyngitis in Adults
• Lacks of unique clinical features for any
causative agents
• The objective in evaluating a patient with
pharyngitis is to identify those with GAS
pharyngitis.
• Algorithms to approach this problem rely either
upon
– a clinical prognostic score,
– rapid antigen testing or both.
Approaches to Acute Pharyngitis in Adults
Clinical predictors
• The Centor criteria have been the most
widely used and accepted. These criteria
including
– exudates
– tender anterior cervical adenopathy
– fever and sore throat by history
– absence of cough and no significant rhinorrhea
Approaches to Acute Pharyngitis in Adults
Predictive Value, Sensitivity and
Specificity of Centor Criteria
• If three or four of these criteria are met, the
positive predictive value are 40 to 60 percent.
• The absence of three or four of the criteria has a
fairly high negative predictive value of 80
percent.
• Both the sensitivity and specificity of this
prediction rule are 75 percent compared to throat
cultures.
• These authorities prefer to restrict treatment to
those with positive rapid antigen testing (RAT) or
culture.
Acute Pharyngitis
• accounted for 2 percent of all ambulatory.
• The major treatable pathogen is group A
streptococcus (GAS), being the cause of
pharyngitis in only approximately 10 percent.
• 73 percent of adults got antibiotics.
• 68 percent of these were more expensive,
broader spectrum agents than those
recommended in practice guidelines.
• Represent the major causes of antibiotic abuse.
Causes of Pharyngitis
• Major causes of pharyngitis is viral agents
including
– influenza, parainfluenza, coronavirus, rhinovirus,
adenovirus, enterovirus, herpes simplex virus
(HSV), EBV, and the human immunodeficiency
virus (HIV).
• The most important treatable agent is GAS,
accounting for 10 percent of cases.
• Other bacterial agents that may cause
pharyngitis include:
– Mycoplasma pneumoniae, Chlamydia
pneumoniae, Neisseria gonorrhoeae, and
Corynebacterium diphtheriae.
An Estimated Distributions of
Organisms in All Age Groups
•
•
•
•
•
•
•
Rhinoviruses — 20 percent
Group A streptococci — 15-30 percent
Coronaviruses — 5 percent
Adenoviruses — 5 percent
Group C streptococci — 5 percent
HSV — 4 percent
Parainfluenza virus — 2 percent
An Estimated Distributions of
Organisms in All Age Groups
•
•
•
•
•
Influenza virus — 2 percent
EBV — <1 percent
HIV — <1 percent
Neisseria gonorrhoeae — <1 percent
Corynebacterium diphtheriae — <1
percent
• Mycoplasma pneumoniae — <1 percent
• Chlamydia pneumoniae — unknown
Distribution of Organisms of 106
Sore Throat Cases from Finland
• Viruses — 25.5 percent
• Non group A beta-hemolytic
streptococci — 17.9 percent
• Mycoplasma pneumoniae — 9.4 percent
• Chlamydia pneumoniae — 8.4 percent
• Group A streptococci — 4.7 percent
• No microbe identified — 31 percent
• Simultaneous identification of two
microbes — 2.8 percent
Approaches to Acute Pharyngitis in Adults
Diagnostic tests
• Throat cultures, the "gold standard" for
diagnosing GAS pharyngitis, can be used
to isolate another pathogen, such as N.
gonorrhoeae.
• Rapid Antigen Test (RAT) have a
sensitivity of 80 to 90 percent and
specificity of 90 to 100 percent.
Approaches to Acute Pharyngitis in Adults
Throat culture
• Relatively insensitive, presumably due to
the methods of specimen collection and
laboratory processing as routinely
performed in clinical practice.
• False positive results due to a one to five
percent carrier rate for the organism.
• With proper techniques in adults, the
sensitivity should be approximately 90
percent and specificity should be 95 to 99
percent.
Approaches to Acute Pharyngitis in Adults
Serology
• a fourfold rising within 2-3 weeks of pair serums
in antistreptolysin (ASO), anti-deoxyribonuclease
B or other streptococcal antibody titer, such as
dehydrogenase
• Most cases of streptococcal pharyngitis show a
rapid rise in titers suggesting an amnestic
response with ASO levels >300 U/ml during acute
infection followed by a peak within two to three
weeks.
Approaches to Acute Pharyngitis in Adults
Management strategies: There are four
reasons to treat a streptococcal pharyngitis
•
•
•
•
To
To
To
To
prevent rheumatic fever
prevent peritonsillar abscess
reduce symptoms
prevent transmission
Approaches to Acute Pharyngitis in Adults
Recommendations
• Using the Centor criteria and the RAT
– Empirically treat patients who have all four
clinical criteria (fever, tonsillar exudate, tender
anterior cervical adenopathy, and absence of
cough).
– Do not treat with antibiotics or perform
diagnostic tests on patients with zero or one
criterion.
– Perform RAT on those with two or three criteria
and use antibiotic treatment only for patients
with positive RAT results
Approaches to Acute Pharyngitis in Adults
• Empiric treatment of all patients with
three or four Centor criteria results in
unnecessary antibiotic exposure to at least
50 percent.
• The Infectious Diseases Society of America
recommend antibiotics only if there is a
positive RAT or culture.
– This criterion will result in undertreatment of
10 to 20 percent, but the consequences of
undertreatment in adults are nil.
Approach to the patient with a
negative evaluation for GAS
• Acute pharyngitis will resolve in most
adults without sequelae.
• Symptomatic treatment, including
antipyretics, fluids, and gargles, can be
helpful.
• In the vast majority of patients, no further
diagnostic measures are required.
CASE 2
 This
52 year-old man developed
cellulitis following trauma to his right
leg. What does the Gram stain of the
purulent drainage from this wound
show?
Gram stain of purulent discharge from the wound
CASE 3
 This
swab was obtained from a 43 yearold female, who had an erythematous,
draining abdominal wound (and underlying
abdominal abscess) after surgery for a
ruptured appendix. What does the Gram
stain show?
Gram stain of erythematous, draining abdominal wound
CASE 4
 This
specimen was aspirated from a
bullous lesion present on the arm of a 21
year-old male intravenous drug user. What
does the Gram stain show?
Gram stain from a bullous lesion on the arm
Culture on blood agar
Necrotic muscle with Clostridium, H and E stain
Tissue Gram Stain of Muscle Biopsy
CASE 5
 A 38
year-old woman developed cellulitis
several hours after being bitten by her cat.
 What does the Gram stain of the purulent
drainage from the wound show?
Gram Stain of Purulent Discharge from the Wound
CASE 6
 This
82 year-old female presented with
vesicular lesions in a dermatomal
distribution.
 What does a Tzanck preparation from a
skin lesion show?
Tzanck Preparation from the Base of Vesicular Lesion
CASE 7
 This
38 year-old Southeast Asian
presented with extensive papular skin
lesions.
 What does an acid-fast stain of a skin
biopsy show?
Modified Acid Fast Stain of Skin Biopsy
Usual Mean MICs for Penicillins against Cocci
Organism
Pen-G Pen-V Amox /Ampi Oxaciln
S. pneumoniae
0.01
0.02
0.02
0.04
S. pyogenes
0.005
0.01
0.02
0.04
S. agalactiae
0.005
0.01
0.02
0.06
S. viridans
0.01
0.01
0.05
0.1
E. faecalis
3.0
6.0
1.5
> 25
Peptostreptococcus
0.2
0.5
0.2
20.6
Staph. aureus
Penicillinase-negative
Penicillinase-positive
0.02
> 25
0.02
> 25
0.05
> 25
0.3
0.4
Staph. epidermidis
0.02
0.02
0.05
0.2
Neisseria gonorrhoeae
0.01
0.1
0.3
12.0
Neisseria meningitidis
0.05
0.25
0.05
6.0
Activity of Penicillins against selected Bacilli and
anaerobic Organisms
Organism
Mean MICS (ug/ml)
Pen G
Amox /
Ampi
Oxaciln
Clostridium perfringens
0.5
0.05
> 0.5
Corynebacterium diphtheriae
0.1
0.02
> 0.1
Listeria monocytogenes
0.5
0.5
> 4.0
Haemophilus influenzae
0.8
0.5
> 25
Prevotella melaninogenica
0.5
0.5
> 25
Fusobacterium nucleatum
0.5
0.1
> 100
Bacteroides fragilis
32
32
> 500
Activity of Penicillins against Enterobacteriaceae and Pseudomonas
Organism
Mean MIC (ug/ml)
Pen G
Amox/ Ampi
Oxaciln
Escherichia coli
100
3
> 1000
Proteus mirabilis
50
3
> 1000
Klebsiella spp.
> 400
200
> 1000
Enterobacter spp.
> 500
> 500
> 1000
Citrobacter diversus
> 500
100
> 1000
Citrobacter freundii
> 500
50
> 1000
Serratia
> 500
> 500
> 1000
Salmonella
10
1.5
> 1000
Shigella
20
1.5
> 1000
Proteus vulgaris
> 500
> 500
> 1000
Providencia
> 500
> 500
> 1000
Morganella
> 500
200
> 1000
Pseudomonas, other
> 500
> 500
> 500
Acinetobacter
> 500
250
> 1000
Pharmacokinetic Properties of Penicillins
Antibiotic
Oral
Food
Absorb Decrease
Serum
Level
Total
Serum T1/2
Free Ccr>90 Ccr<10
Pen G
20
Yes
2
0.9
0.5
10
Pen V
60
No
4
0.8
1
4
Cloxacillin
50
Yes
6
0.6
0.5
1
Ampicillin
40
Yes
3.5
2.9
1
8
Amoxicillin
75
No
7.5
6.2
1
8
500 mg is taken orally
In Vitro Antibacterial Activity of Selected Oral Cephalosporins
MIC90
Organism
Cephalexin
Cefaclor
Cefuroxime Cefdinir
S. pneumoniae
2
0.5
< 0.06
0.03
S. agalactiae
2
2
< 0.12
0.03
S. pyogenes
2
0.5
< 0.06
0.015
Staph. aureus
4
4
4
0.5
H. influenzae
8
8
0.5
0.25
N. gonorrhoeae
2
1
0.25
0.03
Moraxella catarrhalis
4
1
1
0.12
E. coli
> 16
> 16
8
2
Citrobacter diversus
4
0.5
4
0.25
Klebsiella spp
> 16
> 16
2
4
P. mirabilis
16
1
2
0.12
Salmonella spp.
> 16
16
4
0.5
Shigella spp.
> 16
16
2
0.5
Activity of Amoxicillin-Clavulanate against AmoxicillinResistant Organisms
Organism
Amoxicillin
Augmentin
Staphylococcus aureus
256
1.0
Staphylococcus epidermidis
256
2.0
Staphylococcus aureus (MRSA)
256
16.0
Haemophilus influenzae
64
0.5
Branhamella catarrhalis
16
0.25
Neisseria gonorrhoeae
128
1.0
> 256
8.0
128
4.0
Proteus mirabilis
> 256
4.0
Proteus vulgaris
> 256
2.0
32
0.5
> 128
> 128
Escherichia coli
Klebsiella pneumoniae
Bacteroides fragilis
Enterobacter, Citrobacter, Serratia spp. and
Pseudomonas aeruginosa
Vitro Synergism of an Aminoglycoside Combined
with a Cell Wall-Active Antimicrobial
Organism
Aminoglycosides
Cell Wall-Active Drugs
Enterobacteriaceae Gentamicin,
tobramycin,
amikacin
Piperacillin,
cephalothin, cefoxitin,
cefotaxime
Pseudomonas
aeruginosa
Gentamicin,
tobramycin,
amikacin,
netilmicin,
sisomicin
Antipseudomonal
penicillins, aztreonam,
ceftazidime, imipenem
Listeria
monocytogenes
Streptomycin,
gentamicin
Penicillin, ampicillin,
imipenem
Listeria
monocytogenes
Gentamicin,
tobramycin
Vancomycin,
teicoplanin
Corynebacteria,
group JK
Gentamicin,
tobramycin
Vancomycin,
teicoplanin
Vitro Synergism of an Aminoglycoside Combined
with a Cell Wall-Active Antimicrobial
Organism
Aminoglycosides
Cell Wall-Active Drugs
Enterococci
Streptomycin,
Penicillin, ampicillin,
kanamycin,
carbenicillin, nafcillin,
gentamicin,
vancomycin
tobramycin, netilmicin,
sisomicin, amikacin
S. viridans
Streptomycin
Penicillin
S. pyogenes
Gentamicin
Penicillin, ampicillin
Nafcillin, oxacillin,
S. aureus, MSSA Kanamycin,
gentamicin,
cephalothin, vancomycin
tobramycin, netilmicin,
sisomicin
S. aureus, MRSA Gentamicin,
S. epidermidis,
tobramycin
MSSE, MRSE
Teicoplanin (+ rifampicin)
Vancomycin (+ rifampicin
Empirical Indications for Aminoglycosides
Type of Infection
Example (s)
Initial Use in
Combination
with Other
Antimicrobials
Bacteremia, possible
Fever without obvious source
Yes
Burn wound
Burn wound infection
Yes
Endocarditis, infective Streptococcal, enterococcal,
staphylococcal
Yes
Intra-abdominal
Appendicitis, diverticulitis,
cholecystitis, peritonitis
Yes
Meningitis
Post-trauma, postoperative
Yes
Neutropenia and fever Post-chemotherapy
Yes
Ocular
Yes
Endophthalmitis
Empirical Indications for Aminoglycosides
Initial Use in
Combination
with Other
Antimicrobials
Type of Infection
Example (s)
Osteomyelitis/septic
arthritis
Post operative or post-trauma
Yes
Otitis
Malignant external otitis in a
diabetic
Yes
Pneumonia
Respirator-associated
pneumonia
Yes
Pyelonephritis
Patients with chronic Foley
catheter infection
Yes
Sexually transmitted
disease
Pelvic inflammatory disease
Yes
Skin-subcutaneous
tissue
Infected diabetic foot
Yes
MICs of Tetracycline and Doxycycline for
Common Aerobic Bacteria
Organism
No. of Antibiotic
Strains
Cumulative Percentage
Inhibited by Indicated
Concentrations (ug/ml)
1.6
3.2
Neisseria
gonorrhoeae
25
Tetracycline
Doxycycline
85
80
88
92
Neisseria
meningitidis
10
Tetracycline
-
100
Pseudomonas
pseudomallei
10
Tetracycline
60
100
Major Indications for the Tetracyclines
Borrelia burgdorferi (Lyme disease, early)
Borrelia recurrentis (relapsing fever)
Brucellosis (with gentamicin in seriously ill patients
Calymmatobacterium granulomatis (granuloma inguinale)
Chlamydial infections
Chlamydia pneumoniae (TWAR strain)
Epididymitis, acute (sexually transmitted form)
Inclusion conjunctivitis (adult)
Lymphogranuloma venereum
Ornithosis, psittacosis
Trachoma
Urethral, endocervical, or rectal infections in adults
Ehrlichia
Major Indications for the Tetracyclines
Helicobacter pylori (plus metronidazole plus bismuth
subsalicylate)
PID (acute, in combination with other antibiotics)
(doxycycline)
Pseudomonas mallei (glanders) (streptomycin with a
tetracycline)
Rickettsial infections (some prefer chloramphenicol for severe
infections)
Q fever
Rickettsial pox
Rocky Mountain spotted fever
Typhus fever
Urethritis, nonspecific
Urethral syndrome, acute
Vibrio cholerae (cholera)
Vibrio parahamolyticus
Activity of Chloramphenicol against Selected Bacteria
Bacteria
No. of Cumulative Percentage
Strains Inhibited at Indicated
Concentration (ug/ml)
3.2
6.4
Aerobic Bacteria
Gram positive
S. pyogenes
303
92
99
Streptococci group B
146
85
99
Viridans streptococci
193
60
90
S. pneumoniae
78
50
100
Bacteria
No. of
Strains
Cumulative Percentage
Inhibited at Indicated
Concentration (ug/ml)
3.2
6.4
Aerobic Bacteria
Gram negative
Haemophilus influenzae
17
100
-
Neisseria meningitidis
7
100
-
Neisseria gonorrhoeae
106
100
-
Salmonella typhi
81
50
95
S. paratyphi A
31
28
97
Shigella spp.
44
75
90
Brucella spp.
25
92
100
P. pseudomallei
10
0
0
Bordetella pertussia
31
97
97
Activity of Chloramphenicol against Selected Bacteria
No. of
Strains
Bacteria
Anaerobic Bacteria
Cumulative Percentage
Inhibited at Indicated
Concentration (ug/ml)
3.2
6.4
Gram positive
Peptococcus spp.
145
97
98
Peptostreptococcus spp.
72
96
100
Propionibacterium acnes
16
100
-
Eubacterium lentum
14
71
100
Clostridium perfringens
34
100
-
Clostridium spp.
17
88
100
Veillonella spp
13
100
-
Bacteroides fragilis
195
23
98
Prevotella melaninogenica
29
96
100
Fusobacterium spp.
18
89
100
Gram negative
Indications for Chloramphenicol
Indications
Comments
Therapy of Choice: none
Effective Alternative Therapy
Bacterial meningitis
Haemophilus influenzae
Streptococcus pneumoniae
Neisseria meningitidis
Brain abscess
Chlamydia psittaci (psittacosis)
Clostridium perfringens
Ehrlichiosis
For penicillin-allergic
patients
Indications for Chloramphenicol
Indications
Comments
Rickettsial infections
Rocky Mountain spotted fever
Typhus (murine)
Scrub typhus
Tick-bite fever
Q fever
Preferred by some when
patients require parenteral
therapy, during pregnancy,
and for young children
Pseudomonas mallei
Used with streptomycin
Pseudomonas pseudomallei
Used with doxycycline
Typhoid fever and invasive
salmonellosis
Strains in some areas may
be chloramphenicolresistant; not used for
gastroenteritis or carrier
state.
Vibrio vulnificus cellulites an/or
sepsis
In Vitro Activity Susceptibilities to Erythromycin,
Azithromycin, and Clarithromycin
Organism
S. pneumoniae to penicillin
MIC < 0.06 ug/ml
MIC 0.12 – 1.0 ug/ml
MIC > 2 ug/ml
Erythromyc Azithromyc Clarithromyc
in
in
in
MIC 90
MIC 90
MIC 90
0.06
0.06
> 128
0.125
0.125
> 128
0.06
0.03
> 128
S. pyogenes
0.03 - 4
0.12 - 4
0.012 – 2
S. agalactiae
0.03 – 0.25
0.12 – 0.5
0.03 – 0.25
Viridans streptococci
> 3.1
16
> 1.6
Enterococci
> 100
> 32
> 32
Staphylococcus aureus
Methicillin-sensitive
Methicillin-resistant
> 128
> 128
>128
> 128
> 128
> 128
Staphylococcus epidermidis
> 128
> 128
> 128
In Vitro Activity Susceptibilities to Erythromycin,
Azithromycin, and Clarithromycin
Organism
Corynebacterium diphtheriae
Erythromy Azithromyci Clarithromyc
cin
n
in
MIC 90
MIC 90
MIC 90
3.1
-
-
Listeria monocytogenes
0.25 – 4
2-4
0.12 - 2
Moraxella catarrhalis
0.25 - 2
<0.03 – 0.5
0.12 - 1
2 - 32
0.25 - 4
2 - 16
0.03
0.06 – 0.12
0.03
N. gonorrhoeae
0.25 - 2
0.03 – 0.25
0.25 - 2
N. meningitidis
1.6
0.12
-
Campylobacter jejuni
1-4
0.12 – 0.5
1-8
Helicobacter pylori
0.25
0.25
0.03
H. influenzae
Bordetella pertussis
In Vitro Activity Susceptibilities to Erythromycin,
Azithromycin, and Clarithromycin
Organism
Erythromyci
n
MIC 90
Mycoplasma pneumoniae
0.004 – 0.02
0.01 – 0.12
0.03 – 0.5
Chlamydia trachomatis
0.06 - 2
0.12- 0.25
0.008 - 0.125
Chlamydia pneumoniae
0.5
0.5
0.5
Legionella pneumophila
0.5 - 2
0.25 - 2
0.25
Bacteroides fragilis
4 - 32
2- 8
2-8
Peptococcus,
Peptostreptococcus
2 - > 32
2-4
4 - > 32
1
0.25 – 0.78
05 - 2
< 0.03 – 0.03
0.03 – 0.15
0.03 – 0.25
Clostridium perfringens
Proprionibacterium acnes
Azithromyc Clarithromyc
in
in
MIC 90
MIC 90
Major Indications for Use of Erythromycin
Infection in Which
Erythromycin is the Drug of
First Choice
Alternative Drug
Mycoplasma pneumoniae
A fluoroquinolone
Legionella pneumonia
Doxycycline + rifampin, or
trimethoprim-sulfamethoxazole
Diphtheria
Penicillin G
Pertussis
Penicillin G
Chlamydia trachomatis
pneumonia or conjunctivitis
Sulfisoxazole
Prevention of infection after
colorectal surgery
Parenteral cephalosporin
Campylobacter jejuni
gastroenteritis
A tetracycline
Bacillary angiomatosis
Doxycline
Major Indications for Use of Erythromycin
Infection in Which
Erythromycin is an Important
Alternative Drug
Drug of First Choice
Groups A, C, G streptococcal
infection
Penicillin G
S. pneumoniae
Penicillin G, ceftriaxone, or
cefotaxime
C. pneumonia (TWAR) infection
A tetracycline
Rheumatic fever prophylaxis
Penicillin G
Anthrax
Penicillin G
Lymphogranuloma venereum
Tetracycline
Chancroid
Azithromycin or ceftriaxone
Chlamydia trachomatis Urethritis,
cervicitis
Azithromycin or tetracycline
Acne vulgaris
Tetracycline PO and a number of
topical drugs
In Vitro Susceptibilities to Clindamycin
Organism
MIC (ug/ml)
Range
Median
S. pneumoniae
0.002 – 0.04
0.01
S. pyrogenes
0.02 – 0.1
0.04
Viridans
streptococci
0.005 – 0.04
0.02
Enterococcus
12.5 - > 100
100
Staphylococcus
aureus
0.04 - > 100
0.1
Staphylococcus
epidermidis
0.1 > 100
0.1
Clostridium
perfringens
< = 0.1 – 8
0.8
In Vitro Susceptibilities to Clindamycin
Organism
MIC (ug/ml)
Range
Median
N. gonorrhoeae
0.01 – 6.3
3.1
N. Meningitidis
6.3 – 25
12.5
H. influenzae
0.4 – 50
12.5
Bacteroides fragilis
< = 0.125 - > 256
0.25
Bacteroides
melaninogenicus
< = 0.1 - 1
< = 0.1
Fusobacterium spp.
< = 0.5
< = 0.5
Peptococcus spp.
< = 0.1 - > 100
< = 0.5
Peptostreptococcus spp.
< = 0.1 – 0.8
< = 0.5
Mycoplasma pneumoniae
1.6 - 3.1
3.1
In Vitro Activity of Sulfonamides against
Representative Organisms
Organism
Range of MIC
(ug/ml)
Gram – positive organisms
Staphylococcus aureus
8 – 64
Streptococcus pneumoniae
4 - 128
Streptococcus pyogenes
0.5 - 16
Enterococcus faecalis
25 - 250
Corynebacterium diphtheriae
25 - 75
Listeria monocytogenes
3 - 75
Bacillus anthracis
12 - 100
In Vitro Activity of Sulfonamides against
Representative Organisms
Organism
Range of MIC
(ug/ml)
Gram – negative organisms
Escherichia coli
4 – 64
Klebsiella spp.
8 -128
Proteus mirabilis
Serratia marcescens
Salmonella spp.
8 – 128
25 - > 1000
16 – 128
Shigella spp.
2 – 32
Haemophilus influenzae
1 - 16
Neisseria gonorrhoeae
4 - 32
Neisseria meningitidis
0.25 - > 10
Pseudomonas aeruginosa
> 100 - 200
In Vitro Activity of Sulfonamides against
Representative Organisms
Organism
Range of MIC
(ug/ml)
Other organisms
Chlamydia trachomatis
Nocardia asteroides
0.1
2 - 16
In Vitro Activity of Trimethoprim against
Representative Organisms
Range of MIC (ug/ml)
Organism
alone
With SMX
0.15 -2
0.04 – 1.6
Staphylococcus epidermidis
0.02
-
Streptococcus pneumoniae
0.004 - 5
0.05 – 1.5
Streptococcus pyogenes
0.02 - 1
0.015 – 0.4
Enterococcus faecalis
0.15 – 0.5
0.015 – 0.4
Corynebacterium diphtheriae
0.15 – 0.5
0.05 – 0.15
Listeria monocytogenes
0.05 – 1.5
0.015 – 0.15
Clostridium perfringens
2 - 50
-
Propionibacterium acnes
0.07
-
Gram – positive organisms
Staphylococcus aureus
In Vitro Activity of Trimethoprim against
Representative Organisms
Range of MIC (ug/ml)
Organism
alone
With SMX
Escherichia coli
0.01 - > 5
0.005 - > 5
Klebsiella spp.
0.15 - 5
0.05 – 3.1
0.15 – 1.5
0.05 – 0.15
0.8 - 50
0.4 - 50
Salmonella spp.
0.01 – 0.4
0.05 – 0.15
Shigella spp.
0.4 – 0.8
0.02 – 0.5
Citrobacter freundii
0.2
-
Vibrio cholerae
0.2
-
0.1 – 12.5
0.004 - 50
Gram–negative organisms
Proteus mirabilis
Serratia marcescens
Haemophilus influenzae
In Vitro Activity of Trimethoprim against
Representative Organisms
Range of MIC (ug/ml)
Organism
alone
With SMX
Neisseria gonorrhoeae
0.2 - 128
0.15 – 3.1
Neisseria meningitidis
3.1 -50
0.01 – 1.6
50 - 1000
3.1 - 100
1-2
-
Stenotrophomonas maltophilia
1 - > 32
1 - > 32
Bacteroides fragilis
> = 4.0
-
3 - 100
1.5
20
-
Gram – negative organisms
Pseudomonas aeruginosa
Burkholderia cepacia
Other organisms
Chlamydia trachomatis
Nocardia asteroides
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