What You Need to Know When You What You Need to Know When You Prescribe Fluoroquinolones Fluoroquinolones to to Prescribe Community Patients Community Patients David C. Hooper, M.D. David C. Hooper, M.D. Division of Infectious Diseases Division of Infectious Diseases Infection Control Unit Infection Control Unit Massachusetts General Hospital Massachusetts General Hospital Harvard Medical School Harvard Medical School Boston, Massachusetts Boston, Massachusetts GSK Chair of Infectious Diseases Lesson to Students – Brussels, March 28 th , 2007
Sites of Action of Antimicrobial Sites of Action of Antimicrobial Agents in Clinical Use Agents in Clinical Use Topoisomerase IV Daptomycin (Lipopeptide) Linezolid (Oxazolidinone) Telithromycin (Ketolide) Glycylcyclines Neu HC. Science 1992; 257:1064-73
Fluoroquinolones Available Available Fluoroquinolones in the United States in the United States • Norfloxacin Norfloxacin ( (Noroxin Noroxin) ) • Levofloxacin Levofloxacin ( (Levaquin Levaquin) ) • • 1986 (PO) 1996 (IV & PO) 1986 (PO) 1996 (IV & PO) • Ciprofloxacin ( Ciprofloxacin (Cipro Cipro) ) • Gatifloxacin Gatifloxacin ( (Tequin Tequin) ) • • 1987 (PO), 1990 (IV) 1999 (IV & PO) 1987 (PO), 1990 (IV) 1999 (IV & PO) • Moxifloxacin Moxifloxacin ( (Avelox Avelox) ) • Ofloxacin Ofloxacin ( (Floxin Floxin) ) • • 1990 (PO), 1992 (IV) 1999 (PO), 2001 (IV) 1990 (PO), 1992 (IV) 1999 (PO), 2001 (IV) • Gemifloxacin Gemifloxacin ( (Factive Factive) ) • 2003 (PO) 2003 (PO)
Fluoroquinolone Structures Gemifloxacin
Properties of Newer Quinolones Properties of Newer Quinolones • Broad spectrum activity • Broad spectrum activity – Gram-negative bacteria – Gram-negative bacteria – Improved against Gram-positive bacteria – Improved against Gram-positive bacteria – Improved against Anaerobes – Improved against Anaerobes • Once or twice daily dosing • Once or twice daily dosing • Some with apparent reduced risk of • Some with apparent reduced risk of selection of resistance selection of resistance
Fluoroquinolones Fluoroquinolones Spectrum of Activity Spectrum of Activity • Enterobacteriaceae Enterobacteriaceae • • Haemophilus Haemophilus spp spp. . Neisseria Neisseria spp spp. . • • Legionella Legionella, , Mycoplasma Mycoplasma, Chlamydia , Chlamydia • [Levofloxacin Levofloxacin, , Gatifloxacin Gatifloxacin, , [ Moxifloxacin] ] Moxifloxacin • Pseudomonas Pseudomonas aeruginosa aeruginosa [Ciprofloxacin, [Ciprofloxacin, • Levofloxacin] ] Levofloxacin
Fluoroquinolones Fluoroquinolones Spectrum of Activity Spectrum of Activity • Staphylococci (MSSA, MSSE) [ Staphylococci (MSSA, MSSE) [Levofloxacin Levofloxacin, , • Gatifloxacin, , Moxifloxacin Moxifloxacin, , Gemifloxacin Gemifloxacin] ] Gatifloxacin • Streptococci (+/ Streptococci (+/- - enterococci enterococci) [ ) [Levofloxacin Levofloxacin, , • Gatifloxacin, , Moxifloxacin Moxifloxacin, , Gemifloxacin Gemifloxacin] ] Gatifloxacin • Anaerobes [ Anaerobes [Gatifloxacin Gatifloxacin, , Moxifloxacin Moxifloxacin] ] • • Mycobacteria Mycobacteria ( ( M. tuberculosis, M. M. tuberculosis, M. kansasii kansasii, , • M. fortuitum fortuitum ) [Ciprofloxacin, ) [Ciprofloxacin, Levofloxacin Levofloxacin, , M. Gatifloxacin, , Moxifloxacin Moxifloxacin] ] Gatifloxacin
General Clinical Uses of Fluoroquinolones General • Urinary Tract Infections Urinary Tract Infections • • Prostatitis Prostatitis • • Sexually Transmitted Diseases Sexually Transmitted Diseases • • Gastroenteritis Gastroenteritis • • Intraabdominal Intraabdominal Infections Infections • • Respiratory Tract Infections Respiratory Tract Infections • • Bone & Joint Infections Bone & Joint Infections • • Skin & Soft Tissue Infections Skin & Soft Tissue Infections • • Other Broad Uses in Hospitalized Patients Other Broad Uses in Hospitalized Patients •
General Clinical Uses of Fluoroquinolones • Urinary Tract Infections Urinary Tract Infections • • Prostatitis Prostatitis • • Sexually Transmitted Diseases Sexually Transmitted Diseases • • Gastroenteritis Gastroenteritis • • Intraabdominal Intraabdominal Infections Infections • • Respiratory Tract Infections Respiratory Tract Infections • • Bone & Joint Infections Bone & Joint Infections • • Skin & Soft Tissue Infections Skin & Soft Tissue Infections • • Other Broad Uses in Hospitalized Patients Other Broad Uses in Hospitalized Patients •
Community- -Acquired Acquired Community Pneumonia Pneumonia Annually: Annually: • 2 2- -3 Million Cases 3 Million Cases • • ~10 Million Physician Visits ~10 Million Physician Visits • • 500,000 Hospitalizations 500,000 Hospitalizations • – 258 per 100,000 population 258 per 100,000 population – ≥ 65 962 per 100,000 persons ≥ – 962 per 100,000 persons 65 yo yo – • 45,000 Deaths 45,000 Deaths •
Microbial Causes of Community- - Microbial Causes of Community Acquired Pneumonia Acquired Pneumonia • Streptococcus • Mycoplasma Streptococcus pneumoniae pneumoniae Mycoplasma pneumoniae pneumoniae • • • Haemophilus Haemophilus influenzae influenzae • Chlamydia Chlamydia pneumoniae pneumoniae • • • Moraxella Moraxella catarrhalis catarrhalis • Legionella Legionella spp spp. . • • • Staphylococcus Staphylococcus aureus aureus • Influenza virus Influenza virus • • • Klebsiella Klebsiella pneumoniae pneumoniae • Others: Others: mycobacteria mycobacteria, fungi, , fungi, • • Nocardia spp spp., ., Nocardia • Other Gram Other Gram- -negative bacilli negative bacilli • Pneumocystis carinii carinii , other , other Pneumocystis • Anaerobic bacteria Anaerobic bacteria • viruses viruses (aspiration) (aspiration) • None found ~ 50% None found ~ 50% •
Streptococcus pneumoniae pneumoniae Streptococcus Otitis media media 7,000,000 cases Otitis 7,000,000 cases Pneumonia 500,000 cases Pneumonia 500,000 cases Bacteremia 50,000 cases Bacteremia 50,000 cases Meningitis 3,000 cases Meningitis 3,000 cases Deaths 40,000 Deaths 40,000 Mortality rate Mortality rate for bacteremia bacteremia 30 - - 40% 40% for 30 United States data from CDC United States data from CDC
Penicillin- -Non Non- -Susceptible Susceptible Penicillin pneumoniae in the in the Streptococcus pneumoniae Streptococcus United States United States Isolates Resistant to Isolates Resistant to 30 25 Penicillin* (%) Penicillin* (%) 20 15 10 5 0 1979- 1991- 1996 1998 1987 92 Year MIC 0.1 - - 1.0 1.0 * MIC 0.1 * µg/ml g/ml µ Applebaum PC et al. Clin Infect Dis. 1992;15:77 ≥ (intermediate) + ≥ (intermediate) + Breiman RF et al. JAMA. 1994;271:1831 2.0 µ µg/ml (high g/ml (high- - 2.0 Doem GV et al. Antimicrob Ag Chemother. 1996;40:1208 level) resistance level) resistance Whitney CG et al. N. Engl. J. Med. 2000;343:1917
Cross Resistance Among Penicillin- -Resistant Resistant Cross Resistance Among Penicillin Strains of Streptococcus Streptococcus pneumoniae pneumoniae Strains of Antimicrobial % Resistant to Other Antimicrobial Antimicrobial % Resistant to Other Antimicrobial Penicillin Penicillin Penicillin Penicillin Penicillin Penicillin Susceptible Intermediate Resistant Susceptible Intermediate Resistant (n=2636) (n=356, 10% 10%) (n=483, ) (n=483, 14% 14%) ) (n=2636) (n=356, Amoxicillin 0.0 1.8 82.2 Amoxicillin 0.0 1.8 82.2 Cefuroxime 0.1 34.8 100 Cefuroxime 0.1 34.8 100 Cefotaxime 0.0 2.8 42.4 Cefotaxime 0.0 2.8 42.4 Meropenem 0.0 0.8 52.0 Meropenem 0.0 0.8 52.0 Erythromycin 3.2 35.1 61.3 Erythromycin 3.2 35.1 61.3 TMP- -SMX SMX 6.6 49.4 92.3 TMP 6.6 49.4 92.3 Tetracycline 1.3 19.1 25.5 Tetracycline 1.3 19.1 25.5 Whitney CG et al. N. Engl. J. Med. 2000;343:1917-24
Cross Resistance Among Penicillin- -Resistant Resistant Cross Resistance Among Penicillin Strains of Streptococcus Streptococcus pneumoniae pneumoniae Strains of Antimicrobial % Resistant to Other Antimicrobial Antimicrobial % Resistant to Other Antimicrobial Penicillin Penicillin Penicillin Penicillin Penicillin Penicillin Susceptible Intermediate Resistant Susceptible Intermediate Resistant (n=2636) (n=356) (n=483) (n=2636) (n=356) (n=483) Chloramphenicol 0.4 6.7 14.7 Chloramphenicol 0.4 6.7 14.7 Clindamycin 0.5 10.7 12.2 Clindamycin 0.5 10.7 12.2 Rifampin 0.2 0.0 0.2 Rifampin 0.2 0.0 0.2 Levofloxacin 0.1 0.3 0.7 Levofloxacin 0.1 0.3 0.7 Quinupristin- - Quinupristin dalfopristin 0.0 0.6 0.2 dalfopristin 0.0 0.6 0.2 Whitney CG et al. N. Engl. J. Med. 2000;343:1917-24
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