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Case DiscussionCase Discussion
Objective: Antibiotic usages in ambulatory medicine
Topics
1. General Principles of Antibiotic Usages
2. Case Discussion
3. Conclusion
Antibiotic Usages in Ambulatory Antibiotic Usages in Ambulatory
CaresCares • 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 Antibiotic Usages in Ambulatory
CaresCares 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 In Vitro Results of Antimicrobial CombinationsCombinations
Empirical Indications for AminoglycosidesType 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 Endophthalmitis Yes
Empirical Indications for AminoglycosidesType of Infection Example (s) Initial Use in
Combination with Other Antimicrobials
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 S. epidermidis,
MSSE, MRSE
Gentamicin, tobramycin
Teicoplanin (+ rifampicin)Vancomycin (+ rifampicin
In Vitro Activity of Trimethoprim against Representative Organisms
Range of MIC (ug/ml)
Organism alone With SMX
Gram – positive organisms
Staphylococcus aureus 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 -
In Vitro Activity of Trimethoprim against Representative Organisms
Range of MIC (ug/ml)
Organism alone With SMX
Gram–negative organisms
Escherichia coli 0.01 - > 5 0.005 - > 5
Klebsiella spp. 0.15 - 5 0.05 – 3.1
Proteus mirabilis 0.15 – 1.5 0.05 – 0.15
Serratia marcescens 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 -
Haemophilus influenzae 0.1 – 12.5 0.004 - 50
In Vitro Activity of Trimethoprim against Representative Organisms
Range of MIC (ug/ml)
Organism alone With SMX
Gram – negative organisms
Neisseria gonorrhoeae 0.2 - 128 0.15 – 3.1
Neisseria meningitidis 3.1 -50 0.01 – 1.6
Pseudomonas aeruginosa 50 - 1000 3.1 - 100
Burkholderia cepacia 1 - 2 -
Stenotrophomonas maltophilia 1 - > 32 1 - > 32
Bacteroides fragilis > = 4.0 -
Other organisms
Chlamydia trachomatis 3 - 100 1.5
Nocardia asteroides 20 -
Antibiotic Usages in Ambulatory Antibiotic Usages in Ambulatory
CaresCares Antimicrobial Combinations• Disadvantages of the Inappropriate Use
of Antimicrobial Combinations– Antagonism– Cost– Adverse effects
Antibiotic Usages in Ambulatory Antibiotic Usages in Ambulatory
CaresCares 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
Of
Anti-infective Agents
Pharmacodynamics
And
Overview of Interaction of Pharmacokinetics and Pharmacodynamics
Serum Concentration Versus Time Profile of Two-Phase
PharmacokineticsDefinitions 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 1CASE 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 AdultsApproach 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 AdultsApproaches 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
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.
Approaches to Acute Pharyngitis in AdultsApproaches to Acute Pharyngitis in Adults
Acute PharyngitisAcute 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 PharyngitisCauses 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 An Estimated Distributions of Organisms in All Age GroupsOrganisms 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 An Estimated Distributions of Organisms in All Age GroupsOrganisms in All Age Groups
• 2Influenza virus — percent• ppppppp—< 1• ppppppp—< 1• Neisseria gonorrhoeae — <1 percent• Corynebacterium diphtheriae — <1
percent• Mycoplasma pneumoniae — <1 percent• Chlamydia pneumoniae — unknown
Distribution of Organisms of 106 Distribution of Organisms of 106 Sore Throat Cases from FinlandSore 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 AdultsApproaches 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 AdultsApproaches 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 AdultsApproaches 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 AdultsApproaches to Acute Pharyngitis in Adults
Management strategies: There are four reasons to treat a streptococcal pharyngitis
• To prevent rheumatic fever• To prevent peritonsillar abscess • To reduce symptoms• To prevent transmission
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 AdultsApproaches to Acute Pharyngitis in Adults
Approaches to Acute Pharyngitis in AdultsApproaches 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 Approach to the patient with a negative evaluation for GASnegative 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 2CASE 2
This 52 year-old man developed This 52 year-old man developed cellulitis following trauma to his right cellulitis following trauma to his right leg. What does the Gram stain of the leg. What does the Gram stain of the purulent drainage from this wound purulent drainage from this wound show?show?
Gram stain of purulent discharge from the wound
CASE 3CASE 3
This swab was obtained from a 43 year-This swab was obtained from a 43 year-old female, who had an erythematous, old female, who had an erythematous, draining abdominal wound (and underlying draining abdominal wound (and underlying abdominal abscess) after surgery for a abdominal abscess) after surgery for a ruptured appendix. What does the Gram ruptured appendix. What does the Gram stain show?stain show?
Gram stain of erythematous, draining abdominal wound
CASE 4CASE 4
This specimen was aspirated from a This specimen was aspirated from a bullous lesion present on the arm of a 21 bullous lesion present on the arm of a 21 year-old male intravenous drug user. What year-old male intravenous drug user. What does the Gram stain show?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 5CASE 5
A 38 year-old woman developed cellulitis A 38 year-old woman developed cellulitis several hours after being bitten by her cat.several hours after being bitten by her cat.
What does the Gram stain of the purulent What does the Gram stain of the purulent drainage from the wound show?drainage from the wound show?
Gram Stain of Purulent Discharge from the Wound
CASE 6CASE 6
This 82 year-old female presented with This 82 year-old female presented with vesicular lesions in a dermatomal vesicular lesions in a dermatomal distribution.distribution.
What does a Tzanck preparation from a What does a Tzanck preparation from a skin lesion show?skin lesion show?
Tzanck Preparation from the Base of Vesicular Lesion
CASE 7CASE 7
This 38 year-old Southeast Asian This 38 year-old Southeast Asian presented with extensive papular skin presented with extensive papular skin lesions. lesions.
What does an acid-fast stain of a skin What does an acid-fast stain of a skin biopsy show?biopsy show?
Modified Acid Fast Stain of Skin Biopsy
Usual Mean MICs for Penicillins against CocciOrganism -Pen G -Pen V Amox /Ampi Oxacil
n
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
0.30.4
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
Pseudomonas aeruginosa > 500 > 500 > 1000
Pharmacokinetic Properties of Penicillins
Antibiotic Oral Absorb
Food Decrease
Serum Level
Serum T1/2
Total 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 CephalosporinsMIC90
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 Amoxicillin-Resistant 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
Escherichia coli > 256 8.0
Klebsiella pneumoniae 128 4.0
Proteus mirabilis > 256 4.0
Proteus vulgaris > 256 2.0
Bacteroides fragilis 32 0.5
Enterobacter, Citrobacter, Serratia spp. and Pseudomonas aeruginosa
> 128 > 128
Vitro Synergism of an Aminoglycoside Combined with a Cell Wall-Active AntimicrobialOrganism 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, 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 S. epidermidis,
MSSE, MRSE
Gentamicin, tobramycin
Teicoplanin (+ rifampicin)Vancomycin (+ rifampicin
Empirical Indications for AminoglycosidesType 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 Endophthalmitis Yes
Empirical Indications for AminoglycosidesType of Infection Example (s) Initial Use in
Combination with Other Antimicrobials
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 Co mmon Aerobic Bacteria
Organism No. of Strains
Antibiotic Cumulative Percentage Inhibited by Indicated
Concentrations (ug/ml)
1.6 3.2
Neisseria gonorrhoeae
25 TetracyclineDoxycycline
8580
8892
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 TetracyclinesHelicobacter 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
Vibrio vulnificus
Activity of Chloramphenicol against Selected Bacteria
Bacteria No. of Strains
Cumulative Percentage 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 BacteriaGram 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 BacteriaBacteria No. of
StrainsCumulative Percentage Inhibited at Indicated Concentration (ug/ml)
Anaerobic Bacteria 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
Gram negative
Veillonella spp 13 100 -
Bacteroides fragilis 195 23 98
Prevotella melaninogenica 29 96 100
Fusobacterium spp. 18 89 100
Indications for Chloramphenicol
Indications Comments
Therapy of Choice: none
Effective Alternative Therapy
Bacterial meningitis Haemophilus influenzae Streptococcus pneumoniae Neisseria meningitidis
For penicillin-allergic patients
Brain abscess
Chlamydia psittaci (psittacosis)
Clostridium perfringens
Ehrlichiosis
Indications for ChloramphenicolIndications 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 chloramphenicol-resistant; not used for gastroenteritis or carrier state.
Vibrio vulnificus cellulites an/or sepsis
Yersinia pestis
In Vitro Activity Susceptibilities to Erythromycin, Azithromycin, and Clarithromycin
Organism Erythromycin
MIC 90
Azithromycin
MIC 90
Clarithromycin
MIC 90
S. pneumoniae to penicillin MIC < 0.06 ug/ml MIC 0.12 – 1.0 ug/ml MIC > 2 ug/ml
0.060.06
> 128
0.1250.125> 128
0.060.03
> 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 aureusMethicillin-sensitiveMethicillin-resistant
> 128> 128
>128> 128
> 128> 128
Staphylococcus epidermidis > 128 > 128 > 128
In Vitro Activity Susceptibilities to Erythromycin, Azithromycin, and Clarithromycin
Organism Erythromycin
MIC 90
Azithromycin
MIC 90
Clarithromycin
MIC 90
Corynebacterium diphtheriae 3.1 - -
Listeria monocytogenes 0.25 – 4 2 - 4 0.12 - 2
Moraxella catarrhalis 0.25 - 2 <0.03 – 0.5 0.12 - 1
H. influenzae 2 - 32 0.25 - 4 2 - 16
Bordetella pertussis 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
In Vitro Activity Susceptibilities to Erythromycin, Azithromycin, and ClarithromycinOrganism Erythromyci
nMIC 90
Azithromycin
MIC 90
Clarithromycin
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
Clostridium perfringens 1 0.25 – 0.78 05 - 2
Proprionibacterium acnes < 0.03 – 0.03
0.03 – 0.15 0.03 – 0.25
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 ClindamycinOrganism 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 8 – 128
Serratia marcescens 25 - > 1000
Salmonella spp. 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 0.1
Nocardia asteroides 2 - 16
In Vitro Activity of Trimethoprim against Representative Organisms
Range of MIC (ug/ml)
Organism alone With SMX
Gram – positive organisms
Staphylococcus aureus 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 -
In Vitro Activity of Trimethoprim against Representative Organisms
Range of MIC (ug/ml)
Organism alone With SMX
Gram–negative organisms
Escherichia coli 0.01 - > 5 0.005 - > 5
Klebsiella spp. 0.15 - 5 0.05 – 3.1
Proteus mirabilis 0.15 – 1.5 0.05 – 0.15
Serratia marcescens 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 -
Haemophilus influenzae 0.1 – 12.5 0.004 - 50
In Vitro Activity of Trimethoprim against Representative Organisms
Range of MIC (ug/ml)
Organism alone With SMX
Gram – negative organisms
Neisseria gonorrhoeae 0.2 - 128 0.15 – 3.1
Neisseria meningitidis 3.1 -50 0.01 – 1.6
Pseudomonas aeruginosa 50 - 1000 3.1 - 100
Burkholderia cepacia 1 - 2 -
Stenotrophomonas maltophilia 1 - > 32 1 - > 32
Bacteroides fragilis > = 4.0 -
Other organisms
Chlamydia trachomatis 3 - 100 1.5
Nocardia asteroides 20 -
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