《传染病学 Infectious Disease》课程教学资源（MBBS）课程参考书籍教材《Infectious Diseases》

34/ CHAPTER 1 KEY POINTS The first form is dose-related and is commonly observed in patients receiving chloramphenicol 4g or more daily. The reticulocyte count decreases, and ane- About the Tetracyclines mia develops in association with elevated serum iror Leukopenia and thrombocytopenia are also com- 1. Bind to the 30S subunit of the ribosome block monly encountered. These changes reverse when the ing tRNa binding and inhibiting protein synthe- antibiotic is discontinued. The second form of mar sis Bacteriostatic for most gram-positive and row toxicity, irreversible aplastic anemia, is rare, bur gram-negative bacteria usually fatal. This complication can occur weeks or 2. Toxicities include photosensitivity, months after the antibiotic is discontinued. Any patient receiving ramphenicol requires twice weekly monitoring of peripheral blood counts. If the exacerbation of azotemia, vertigo(minocy WBC drops below 2500/mm,, the drug should be cline), and pseudotumor cerebri. 3. Tetracycline can be used for uncomplicated PHARMACOKINETICS nary tract infections. 4. Recommended for brucellosis, Lyme disease, As a result of the much higher incidence of idiosyn hlamydia, and rickettsial infections cratic aplastic anemia associated with oral administra tion as compared with intravenous administration Recommended, in combination with other antibiotics, for pelvic inflammatory disease. parations of chloramphenicol are no lor available in the United States. the drug is well Oral absorption blocked by calcium- and absorbed, and therapeutic serum levels can be magnesium-containing antacids, milk, achieved orally(Table 1. 11). Chloramphenicol metabolized by the liver. It diffuses well into tissues 7. Tigecycline has improved gram-positive and and crosses the blood-brain bar uninflamed as gram-negative coverage, with the exception of well as inflamed meninges. A serum assay is available, Pseudomonas aeruginosa and Proteus. It is approved for complicated intra-abdominal and and serum levels should be monitored in patients with soft-tissue infections hepatic disease, maintaining the serum concentration between10and25μg/mL ANTIMICROBIAL SPECTRUM AND TREATMENT RECOMMENDATIONS demonstrates improved activity against many Chloramphenicol has excellent activity against most resistant nosocomial gram-negative bacteria, gram-positive organisms with the exception of entero- does not effectively cover P aeruginosa or P cocci and S. aureus, as well as many gram-negative species. Tigecycline is approved for complicated intra abdominal and soft-tissue infections Chloramphenicol KEY POINTS CHEMISTRY AND MECHANISMS OF ACTION Chloramphenicol consists of a nitro group on a benzene About Chloramphenicol ring and a side chain containing five carbons. Chloram phenicol uses an energy-dependent mechanism to enter 1. Binds to 50S subunit of the ribosome, blocking bacteria, and once in the cell, binds to the larger 50S tein synthesis; is bacteriostatic. subunit of the 70S ribosome, blocking attachment of 2. Idiosyncratic aplastic anemia has limited the tRNA. It inhibits bacterial protein synthesis, making it use of chloramphenicol; dose-related bone bacteriostatic for most bacteria; however, chlorampheni marrow suppression is another concern. col is cidal for H. influenzae, S. pneumoniae, and 3. Broad spectrum of activity, including Salmo- N nella, Brucella, Bordetella, anaerobes, Rick ettsiae, Chlamydiae, Mycoplasma, and spiro- Tox chetes Probably as result of its binding to human mitochon 4. Can d as alternative therapy in the drial ribosomes, this agent has significant bone mar penicillin-allergic patient. row toxicity(see Table 1.10). Two forms are observed

demonstrates improved activity against many highly resistant nosocomial gram-negative bacteria, but it does not effectively cover P. aeruginosa or Proteus species. Tigecycline is approved for complicated intra￾abdominal and soft-tissue infections. Chloramphenicol CHEMISTRY AND MECHANISMS OF ACTION Chloramphenicol consists of a nitro group on a benzene ring and a side chain containing five carbons. Chloram￾phenicol uses an energy-dependent mechanism to enter bacteria, and once in the cell, binds to the larger 50S subunit of the 70S ribosome, blocking attachment of tRNA. It inhibits bacterial protein synthesis, making it bacteriostatic for most bacteria; however, chlorampheni￾col is cidal for H. influenzae, S. pneumoniae, and N. meningitidis. TOXICITY Probably as result of its binding to human mitochon￾drial ribosomes, this agent has significant bone mar￾row toxicity (see Table 1.10). Two forms are observed. The first form is dose-related and is commonly observed in patients receiving chloramphenicol 4 g or more daily. The reticulocyte count decreases, and ane￾mia develops in association with elevated serum iron. Leukopenia and thrombocytopenia are also com￾monly encountered. These changes reverse when the antibiotic is discontinued. The second form of mar￾row toxicity, irreversible aplastic anemia, is rare, but usually fatal. This complication can occur weeks or months after the antibiotic is discontinued. Any patient receiving chloramphenicol requires twice￾weekly monitoring of peripheral blood counts. If the WBC drops below 2500/mm3 , the drug should be discontinued. PHARMACOKINETICS As a result of the much higher incidence of idiosyn￾cratic aplastic anemia associated with oral administra￾tion as compared with intravenous administration, oral preparations of chloramphenicol are no longer available in the United States. The drug is well absorbed, and therapeutic serum levels can be achieved orally (Table 1.11). Chloramphenicol is metabolized by the liver. It diffuses well into tissues and crosses the blood–brain barrier in uninflamed as well as inflamed meninges. A serum assay is available, and serum levels should be monitored in patients with hepatic disease, maintaining the serum concentration between 10 and 25 g/mL. ANTIMICROBIAL SPECTRUM AND TREATMENT RECOMMENDATIONS Chloramphenicol has excellent activity against most gram-positive organisms with the exception of entero￾cocci and S. aureus, as well as many gram-negative 34 / CHAPTER 1 1. Bind to the 30S subunit of the ribosome, block￾ing tRNA binding and inhibiting protein synthe￾sis. Bacteriostatic for most gram-positive and gram-negative bacteria. 2. Toxicities include photosensitivity, interference with dental enamel formation in children, gas￾trointestinal discomfort, fatty liver changes, exacerbation of azotemia, vertigo (minocy￾cline), and pseudotumor cerebri. 3. Tetracycline can be used for uncomplicated uri￾nary tract infections. 4. Recommended for brucellosis, Lyme disease, chlamydia, and rickettsial infections 5. Recommended, in combination with other antibiotics, for pelvic inflammatory disease. 6. Oral absorption blocked by calcium- and magnesium-containing antacids, milk, and multivitamins. 7. Tigecycline has improved gram-positive and gram-negative coverage, with the exception of Pseudomonas aeruginosa and Proteus. It is approved for complicated intra-abdominal and soft-tissue infections. KEY POINTS About the Tetracyclines 1. Binds to 50S subunit of the ribosome, blocking protein synthesis; is bacteriostatic. 2. Idiosyncratic aplastic anemia has limited the use of chloramphenicol; dose-related bone marrow suppression is another concern. 3. Broad spectrum of activity, including Salmo￾nella, Brucella, Bordetella, anaerobes, Rick￾ettsiae, Chlamydiae, Mycoplasma, and spiro￾chetes. 4. Can be used as alternative therapy in the penicillin-allergic patient. KEY POINTS About Chloramphenicol

ANTI-INFECTIVE THERAPY/ 3 pathogens(Figure 1.5). Chloramphenicol also is very active st spirochetes, as well as Rickettsiae, Chlamydiae, and mycoplasmas COOH Because of its bone marrow toxicity, chloramphe F col is not considered the treatment of choice for Added Potency infection. Alternative, less-toxic agents are available for each indication. For the penicillin-allergic patient chloramphenicol can be used for bacterial meningitis Chloramphenicol can also be used as alternative ther- apy for brain abscess, C perfringens, psittacosis, rick ntain fever, Vibrio vulnificus, and typhoid fever. Figure 1-7. Basic structure of the quinolones Quinolones Tables 1. 14 and 1.15, together with Figure 1.5, summa- rizes the characteristics of the quinolone antibiotics formed daughter cells. The loss of these activi- CHEMICAL STRUCTURE AND MECHANISMS OF ACTION synthesis and results in rapid bacterial death. Kill The quinolones all contain two 6-member rings(see Figure 1.7) with a nitrogen at position I, a carbonyl ToxICITY group at position 4, and a carboxyl group attached The most common side effects are mild anorexia, nau sea,vomiting, and abdominal discomfort(Table 1.10) greatly enhanced by adding fluorine at position 6, and Quinolones can result in arthropathy because of carti gram-negative activity is enhanced by addition of a lage damage and tendonitis. Although rare, this compli cation can be debilitating, but it usually reverses weeks The quinolones inhibit two enzymes critical for dna to months after the quinolone is discontinued. Because synthesis: DNA gyrase, which is important for regulating of concerns about cartilage damage in children the superhelical twists of bacterial DNA, and tope x taton in pediatric patients. Gatifloxacin administra- merase IV, which is responsible for segregating so- quinolones are not recommended for routine adminis- ion can be associated with severe dysregulation of lucose homeostasis and can result in either severe KEY POINTS po-or hyperglycemia. Fluoroquinolones are associ ted with a concentration-dependent delay in cardiac About the Chemistry, Mechanisms of Action, polarization, causing a prolongation of the QT inter al-a condition that can predispose to ventricular and Toxicity of Quinolones tachycardia. In combination with other agents that effect repolarization, moxifloxacin has occasionally been 1. Inhibit bacterial DNa gyrase(important for associated with life-threatening cardiac arrhythmias coiling DNA)and topoisomerase (required to PHARMACOKINETICS segregate DNA to daughter cells). Rapidly cidal, with conce The quinolones are readily absorbed orally, but can als 2. Main side effects are be given intravenously. Ciprofoxacin, levofloxacin, and a)nausea and anorexia gatifloxacin are cleared primarily by the kidneys. Moxi is also partially metabolized by the liver, and b)allergic reactions (most common with gemifloxacin; less common with other gemifloxacin is metabolized primarily by the liver. All quinolones quinolones demonstrate similar tissue penetration being concentrated in prostate tissue, feces, bile, and c) Arthropathy and tendonitis. May damage lung tissue. These drugs tend to be very highly concen d)Gatifloxacin can cause hypo- or hyper SPECTRUM OF ACTIVITY AND glycemia. TREATMENT RECOMMENDATIONS e)Moxifloxacin prolongs the QT interva Ciprofloxacin--Ciprofloxacin is the most potent (Table 1. 15, Figure 1.5).As

pathogens (Figure 1.5). Chloramphenicol also is very active against spirochetes, as well as Rickettsiae, Chlamydiae, and mycoplasmas. Because of its bone marrow toxicity, chlorampheni￾col is not considered the treatment of choice for any infection. Alternative, less-toxic agents are available for each indication. For the penicillin-allergic patient, chloramphenicol can be used for bacterial meningitis. Chloramphenicol can also be used as alternative ther￾apy for brain abscess, C. perfringens, psittacosis, rick￾ettsial infections including Rocky Mountain spotted fever, Vibrio vulnificus, and typhoid fever. Quinolones Tables 1.14 and 1.15, together with Figure 1.5, summa￾rizes the characteristics of the quinolone antibiotics. CHEMICAL STRUCTURE AND MECHANISMS OF ACTION The quinolones all contain two 6-member rings (see Figure 1.7) with a nitrogen at position 1, a carbonyl group at position 4, and a carboxyl group attached to the carbon at position 3. Potency of the quinolones is greatly enhanced by adding fluorine at position 6, and gram-negative activity is enhanced by addition of a nitrogen-containing piperazine ring at position 7. The quinolones inhibit two enzymes critical for DNA synthesis: DNA gyrase, which is important for regulating the superhelical twists of bacterial DNA, and topoiso￾merase IV, which is responsible for segregating newly formed DNA into daughter cells. The loss of these activi￾ties blocks DNA synthesis and results in rapid bacterial death. Killing is concentration-dependent. TOXICITY The most common side effects are mild anorexia, nau￾sea, vomiting, and abdominal discomfort (Table 1.10). Quinolones can result in arthropathy because of carti￾lage damage and tendonitis. Although rare, this compli￾cation can be debilitating, but it usually reverses weeks to months after the quinolone is discontinued. Because of concerns about cartilage damage in children, quinolones are not recommended for routine adminis￾tration in pediatric patients. Gatifloxacin administra￾tion can be associated with severe dysregulation of glucose homeostasis and can result in either severe hypo- or hyperglycemia. Fluoroquinolones are associ￾ated with a concentration-dependent delay in cardiac repolarization, causing a prolongation of the QT inter￾val—a condition that can predispose to ventricular tachycardia. In combination with other agents that effect repolarization, moxifloxacin has occasionally been associated with life-threatening cardiac arrhythmias. PHARMACOKINETICS The quinolones are readily absorbed orally, but can also be given intravenously. Ciprofloxacin, levofloxacin, and gatifloxacin are cleared primarily by the kidneys. Moxi- floxacin is also partially metabolized by the liver, and gemifloxacin is metabolized primarily by the liver. All quinolones demonstrate similar tissue penetration, being concentrated in prostate tissue, feces, bile, and lung tissue. These drugs tend to be very highly concen￾trated in macrophages and neutrophils. SPECTRUM OF ACTIVITY AND TREATMENT RECOMMENDATIONS Ciprofloxacin—Ciprofloxacin is the most potent quinolone for P. aeruginosa (Table 1.15, Figure 1.5). As a ANTI-INFECTIVE THERAPY / 35 1. Inhibit bacterial DNA gyrase (important for coiling DNA) and topoisomerase (required to segregate DNA to daughter cells). Rapidly cidal, with concentration-dependent killing. 2. Main side effects are a) nausea and anorexia. b) allergic reactions (most common with gemifloxacin; less common with other quinolones). c) Arthropathy and tendonitis. May damage cartilage. Not routinely recommended in children. d) Gatifloxacin can cause hypo- or hyper￾glycemia. e) Moxifloxacin prolongs the QT interval. KEY POINTS About the Chemistry, Mechanisms of Action, and Toxicity of Quinolones Figure 1–7. Basic structure of the quinolones

36/ CHAPTER 1 Table 1. 14. Quinolones, Linezolid, Quinupristin/Dalfopristin, Daptomycin, Metronidazole, and Sulfano- mides: Half-Life, Dosing, Renal Dosing, Cost, and Spectrum Antibiotic Dose Dose for reduced Cost Spectrum (trade name (loading/ creatinine clearance maintenance (mL/min) Ciprofloxacin 10-50:q18h PO: SSS Moderately 0q12h,or <10:q24h ⅣV:S-S5 broad 200-400mgⅣq12h Levofloxacin 6-8 500 mg PO or IV q24h 10-50 250 mg q24h PO: SSS Broad <10:250mgq48h Gatifloxacin 6-8 400 mg PO or IV q24h 10-50 200 mg q24h Very broad (Tequin) <10:200mgq24h Moxifloxacin No change required Very broad 7320mgP0q24h10-50:160mgq24h555 Factive) <10:160mgq24h Linezolid 600 mg PO or IV q12h No change required P:S555 ⅣVSss 1.5 7.5 mg/kg IV q8-12h No change required Narrow dalfopristin (Synercid) 4mg/kgⅣq24h <30:q48h Narrow (Cubicin) (soft-tissue infection) aureus bacteremia) Metronidazole 6-14 500 mg PO q8h,or change required 500 mg-1 g Po q12h In severe hepatic fail 15 mg/kg followed by half the dose. 15 mg/kg q12h ed 4 g) 1-2 g Po goh 10-50:1g Moderately q8-12h Broad <10:1gq12-24h 05-1.5gPoq4-6h10-50:05- 15gq8-12h Broad 1005-159912-24h 2-4 tablets g24h or Half the oral dose and 1-2 DS PO q24h reduce the iv dose to Broad 10-50:3-5mg/kgq12-24h 3-5 mg/kg IV g6-12h <10: Don't give Intravenous preparations(daily cost dollars):$=20-70: $$=71-110; $SS=111-150: SSS$= 150-200; SSSS$ 2 200; oral preparations(10- day course cost dollars):5=10-5055=51-100555=101-140:5555=141-18055552180

36 / CHAPTER 1 Table 1.14. Quinolones, Linezolid, Quinupristin/Dalfopristin, Daptomycin, Metronidazole, and Sulfano￾mides: Half-Life, Dosing, Renal Dosing, Cost, and Spectrum Antibiotic Half- Dose Dose for reduced Costa Spectrum (trade name) life (loading/ creatinine clearance (h) maintenance) (mL/min) Ciprofloxacin 4 250–750 mg 10–50: q18h PO: $$$ Moderately (Cipro) PO q12h, or <10: q24h IV: $–$$ broad 200–400 mg IV q12h Levofloxacin 6–8 500 mg PO or IV q24h 10–50: 250 mg q24h PO: $$$ Broad (Levoquin) <10: 250 mg q48h IV: $ Gatifloxacin 6–8 400 mg PO or IV q24h 10–50: 200 mg q24h PO: $$ Very broad (Tequin) <10: 200 mg q24h IV: $ Moxifloxacin 6–8 400 mg PO q24h No change required PO: $$ Very broad (Avelox) IV: $ Gemifloxacin 7 320 mg PO q24h 10–50: 160 mg q24h $$$$$ Broad (Factive) <10: 160 mg q24h Linezolid 5 600 mg PO or IV q12h No change required PO: $$$$$ Narrow (Zyvox) IV: $$$$ Quinupristin/ 1.5 7.5 mg/kg IV q8–12h No change required $$$$$ Narrow dalfopristin (Synercid) Daptomycin 8–9 4 mg/kg IV q24h <30: q48h $$$$–$$$$$ Narrow (Cubicin) (soft-tissue infection) 6 mg/kg IV q24h (Staphylococcus aureus bacteremia) Metronidazole 6–14 500 mg PO q8h, or No change required. $ Narrow (Flagyl, 500 mg–1 g PO q12h In severe hepatic failure, Protostat, 15 mg/kg followed by half the dose. Metronid) 7.5 mg/kg IV q6h or 15 mg/kg q12h (not to exceed 4 g) Sulfisoxazole 1–2 g PO q6h 10–50: 1 g $ Moderately q8–12h Broad <10: 1 g q12–24h Sulfadiazine 0.5–1.5 g PO q 4–6h 10–50: 0.5– $$ Moderately 1.5 g q8–12h Broad <10: 0.5–1.5 g q12–24h Trimethoprim– 2–4 tablets q24h or Half the oral dose, and $ Moderately sulfamethoxazole 1–2 DS PO q24h reduce the IV dose to Broad Trimethoprim: 10–50: 3–5 mg/kg q12–24h 3–5 mg/kg IV q6–12h <10: Don’t give a Intravenous preparations (daily cost dollars): $ = 20–70; $$ = 71–110; $$$ = 111–150; $$$$ = 150–200; $$$$$ ≥ 200; oral preparations (10-day course cost dollars): $ = 10–50; $$ = 51–100; $$$ = 101–140; $$$$ = 141–180; $$$$$ ≥ 180

ANTI-INFECTIVE THERAPY/ 3 Table 1.15. Organisms That May Be Susceptible to the Quinolones Levofloxacin, Gemifloxacin, Gatifloxacin, Moxifloxacin Pseudomonas aeruginosa Same as ciprofloxacin, plus: Proteus spp Streptococcus pneumoniae Providencia Vancomycin-sensitive Enterococcus aImonella, including Sal typhi Strep pyogenes Gatifloxacin and moxifloxacin anaerobes Campylobacter spp Bacillus anthracis Bartonella henselae Neisseria gonorrhoeae of an excellent gram-negative spectrum, thought to include anaerobes. The exact indications xacin is one of the primary antibiotics recom- for these agents are currently evolving. Fear of select for treatment of urinary tract infections. It ing for resistant pathogens has led to their use being concentrates in the prostate and is recommended for treat- restricted in some hospitals. ment of prostatitis. For gonococcal urethritis, it is a useft alternative to ceftriaxone. Ciprofloxacin has been used Oxazolidones(Linezolid effectively for travelet's diarrhea most commonly caused by enterotoxigenic E. coli and Shigella. It is the drug of CHEMISTRY AND MECHANISMS OF ACTION choice for Salmonella typhi(typhoid fever), and it also is The oxazolidones have a unique ring structure con- recommended for treatment of Salmonella gastroenteritis sisting of a 5-member ring containing an oxygen and when antibiotic treatment is necessary. Ciprofloxacin is a nitrogen. The nitrogen connects to a6-member the recommended treatment for cat scratch disease caused ring, and each specific compound has side chains by Bartonella henselae. added to both rings at positions A and B (Figure 1.8) Levofloxacin, Moxifloxacin, Gatifloxacin, and These agents bind to the 50S ribosome at a site simi Gemifloxacin--These agents all demonstrate impro- lar to that used by chloramphenicol. However, unlike ved gram-positive coverage (Table 1. 15, Figure 1.5) chloramphenicol, they do not inhibit the attachment and have been recommended as one of the first-line of tRNA, but instead block the initiation of protein treatments for community-acquired pneumonia in the synthesis by preventing the nearby 30S subunit from otherwise healthy adult who does not require hospital- ization. With the exception of gemifloxacin, the agents can also be used in soft-tissue infection in which a combination of gram-positive and gram-negative uspected. Given the worse toxicity profiles of the three newer agents(moxifloxacin, gat probably be the fluoroquinolone of choice for those fections. Gatifloxacin and moxifloxacin demonstrate moderate in vitro activity against anaerobes and may Figure 1-8. Basic structure of the be considered for the treatment of mixed infections oxazolidones

result of an excellent gram-negative spectrum, ciprofloxacin is one of the primary antibiotics recom￾mended for treatment of urinary tract infections. It concentrates in the prostate and is recommended for treat￾ment of prostatitis. For gonococcal urethritis, it is a useful alternative to ceftriaxone. Ciprofloxacin has been used effectively for traveler’s diarrhea most commonly caused by enterotoxigenic E. coli and Shigella. It is the drug of choice for Salmonella typhi (typhoid fever), and it also is recommended for treatment of Salmonella gastroenteritis when antibiotic treatment is necessary. Ciprofloxacin is the recommended treatment for cat scratch disease caused by Bartonella henselae. Levofloxacin, Moxifloxacin, Gatifloxacin, and Gemifloxacin—These agents all demonstrate impro￾ved gram-positive coverage (Table 1.15, Figure 1.5) and have been recommended as one of the first-line treatments for community-acquired pneumonia in the otherwise healthy adult who does not require hospital￾ization. With the exception of gemifloxacin, these agents can also be used in soft-tissue infection in which a combination of gram-positive and gram-negative organisms is suspected. Given the worse toxicity profiles of the three newer agents (moxifloxacin, gati￾floxacin, and gemifloxacin), levofloxacin should probably be the fluoroquinolone of choice for those infections. Gatifloxacin and moxifloxacin demonstrate moderate in vitro activity against anaerobes and may be considered for the treatment of mixed infections thought to include anaerobes. The exact indications for these agents are currently evolving. Fear of select￾ing for resistant pathogens has led to their use being restricted in some hospitals. Oxazolidones (Linezolid) CHEMISTRY AND MECHANISMS OF ACTION The oxazolidones have a unique ring structure con￾sisting of a 5-member ring containing an oxygen and a nitrogen. The nitrogen connects to a 6-member ring, and each specific compound has side chains added to both rings at positions A and B (Figure 1.8). These agents bind to the 50S ribosome at a site simi￾lar to that used by chloramphenicol. However, unlike chloramphenicol, they do not inhibit the attachment of tRNA, but instead block the initiation of protein synthesis by preventing the nearby 30S subunit from ANTI-INFECTIVE THERAPY / 37 Table 1.15. Organisms That May Be Susceptible to the Quinolones Ciprofloxacin Levofloxacin, Gemifloxacin, Gatifloxacin, Moxifloxacin Pseudomonas aeruginosa Same as ciprofloxacin, plus: Escherichia coli Methicillin-sensitive Enterobacter cloacae Staphylococcus aureus Proteus spp. Streptococcus pneumoniae Providencia Vancomycin-sensitive Enterococcus Salmonella, including Sal. typhi Strep. pyogenes Shigella spp. Gatifloxacin and moxifloxacin: anaerobes Yersinia spp. Campylobacter spp. Bacillus anthracis Mycoplasma pneumoniae Chlamydia spp. Ureaplasma urealyticum Bartonella henselae Neisseria gonorrhoeae Figure 1–8. Basic structure of the oxazolidones

38/ CHAPTER 1 KEY POINTS KEY POINTS About the Specific Quinolones About linezolid 1. Like chloramphenicol, binds to the 50S ribo a)Excellent coverage of Pseudomonas. Also ome subunit; inhibits the initiation of protein covers many other gram-negative organisms including Esch coli, Salmonella, Shigella, Neis- 2. Thrombocytopenia common with treatment seria, and Legionella. xceeding 2 weeks; inhib b)Kills Mycoplasma, Chlamydia, and Ure- ase; avoid tyramine, pseudoephedrine, sero- nin uptake inhibitors. c) Recommended for urinary tract infections 3. Strictly gram-positive activity; bacteriostatic d prostatitis, gonococcal urethritis, trav activity for vancomycin resistant enteroco elers diarrhea, typhoid fever, and salmonella (VRE), and methicillin-resistant Staphylococcus gastroenteritis; used for cat scratch disease ureus. Also has activity against penicillin-resis- 2. Levofloxacin, gatifloxacin, moxifloxacin, gemi- tant Streptococcus pneumoniae. floxacin 4. Recommended for the treatment of vre a)Greater activity against Streptococcus pneu- moniae, covers highly penicillin-resistant b)Also cover methicillin-sensitive Staphyloco does not lower peak levels. An intravenous preparation Cus aureus also available. Linezolid achieves excellent penetratio c)Recommended for community-acquired of all tissue spaces, including the cerebrospinal fuid pneumonia(levofloxacin preferred The drug is partly metabolized by the liver and excreted d) Levofloxacin, gatifloxacin, and moxifloxacin in the urine ecommended for mixed skin infections ANTIMICROBIAL ACTIVITY AND e) Gatifloxacin and moxifloxacin have some- TREATMENT RECOMMENDATIONS what improved anaerobic coverage. f)Gatifloxacin and moxifloxacin recommended Linezolid demonstrates activity only against gram-positive for mixed skin infections ms, it has bacteriostatic vancomycin-resistant Enterococcus faecium and Enterococ- cus faecalis(VRE). This agent is also active against MSSA and MRSA, and has activity against penicillin-resistant forming the 70S initiation complex. The oxazolidones pneumoniae. Linezolid is recommended primarily for Streptogramins ToXICITY Linezolid is the only agent in this class released for use. CHEMICAL STRUCTURE AND MECHANISM OF AcTION Reversible thrombocytopenia has been reported in asso- The streptogramins belong to the macrolide family. ciation with prolonged therapy, and monitoring of They are derived from pristinamycin. Quinupristin platelet count is recommended for patients receiving a peptide derived from pristinamycin IA and dalo- two or more weeks of linezolid. Leukopenia and hepatic pristin is derived from pristinamycin IIB. A combina enzyme elevations have also been reported. Because this tion of 30: 70 quinupristin: dalfopristin has synergistic gent is a weak inhibitor of monoamine oxidase, hyper- activity and has been named Synercid. These two tension has been reported in association with ingestion agents inhibit bacterial protein synthesis by bindir of large amounts of tyramine. Pseudoephedrine and to the 50S bacterial ribosome. Quinupristin inhibits selective serotonin reuptake inhibitors should be pre- peptide chain elongation, and dalfopristin interferes with peptidyl transferase activity PHARMACOKINETICS ToXICITY Linezolid is well-absorbed orally, and peak serum levels Myalgias and arthralgias are the most common and severe are achieved in I to 2 hours. Food slows absorption, but adverse reaction, and they can force discontinuation of

forming the 70S initiation complex. The oxazolidones are bacteriostatic against staphylococcal species and enterococci. TOXICITY Linezolid is the only agent in this class released for use. Reversible thrombocytopenia has been reported in asso￾ciation with prolonged therapy, and monitoring of platelet count is recommended for patients receiving two or more weeks of linezolid. Leukopenia and hepatic enzyme elevations have also been reported. Because this agent is a weak inhibitor of monoamine oxidase, hyper￾tension has been reported in association with ingestion of large amounts of tyramine. Pseudoephedrine and selective serotonin reuptake inhibitors should be pre￾scribed with caution. PHARMACOKINETICS Linezolid is well-absorbed orally, and peak serum levels are achieved in 1 to 2 hours. Food slows absorption, but does not lower peak levels. An intravenous preparation is also available. Linezolid achieves excellent penetration of all tissue spaces, including the cerebrospinal fluid. The drug is partly metabolized by the liver and excreted in the urine. ANTIMICROBIAL ACTIVITY AND TREATMENT RECOMMENDATIONS Linezolid demonstrates activity only against gram-positive organisms. It has bacteriostatic activity against both vancomycin-resistant Enterococcus faecium and Enterococ￾cus faecalis (VRE). This agent is also active against MSSA and MRSA, and has activity against penicillin-resistant S. pneumoniae. Linezolid is recommended primarily for the treatment of VRE. Streptogramins CHEMICAL STRUCTURE AND MECHANISM OF ACTION The streptogramins belong to the macrolide family. They are derived from pristinamycin. Quinupristin is a peptide derived from pristinamycin IA and dalfo￾pristin is derived from pristinamycin IIB. A combina￾tion of 30:70 quinupristin:dalfopristin has synergistic activity and has been named Synercid. These two agents inhibit bacterial protein synthesis by binding to the 50S bacterial ribosome. Quinupristin inhibits peptide chain elongation, and dalfopristin interferes with peptidyl transferase activity. TOXICITY Myalgias and arthralgias are the most common and severe adverse reaction, and they can force discontinuation of 38 / CHAPTER 1 1. Ciprofloxacin: a) Excellent coverage of Pseudomonas. Also covers many other gram-negative organisms including Esch. coli, Salmonella, Shigella, Neis￾seria, and Legionella. b) Kills Mycoplasma, Chlamydia, and Ure￾aplasma. c) Recommended for urinary tract infections and prostatitis, gonococcal urethritis, trav￾eler’s diarrhea, typhoid fever, and Salmonella gastroenteritis; used for cat scratch disease. 2. Levofloxacin, gatifloxacin, moxifloxacin, gemi- floxacin a) Greater activity against Streptococcus pneu￾moniae, covers highly penicillin-resistant strains. b) Also cover methicillin-sensitive Staphylococ￾cus aureus. c) Recommended for community-acquired pneumonia (levofloxacin preferred). d) Levofloxacin, gatifloxacin, and moxifloxacin recommended for mixed skin infections. e) Gatifloxacin and moxifloxacin have some￾what improved anaerobic coverage. f ) Gatifloxacin and moxifloxacin recommended for mixed skin infections. KEY POINTS About the Specific Quinolones 1. Like chloramphenicol, binds to the 50S ribo￾some subunit; inhibits the initiation of protein synthesis. 2. Thrombocytopenia common with treatment exceeding 2 weeks; inhibitor of monoamine oxi￾dase; avoid tyramine, pseudoephedrine, sero￾tonin uptake inhibitors. 3. Strictly gram-positive activity; bacteriostatic activity for vancomycin-resistant enterococci (VRE), and methicillin-resistant Staphylococcus aureus. Also has activity against penicillin-resis￾tant Streptococcus pneumoniae. 4. Recommended for the treatment of VRE. KEY POINTS About Linezolid