Case Discussion Objective: Antibiotic usages in ambulatory medicine Topics 1.General Principles of...

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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