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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 ติดต่อ E-mail : [email protected]