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

24/ CHAPTER 1 Table 1.8. Aminoglycosides: Half-Life, Dosing, Renal Dosing, Cost, and Spectrum Antibiotic Half-life Dose for reduced Cost (trade name creatinine clearance 2 mg/kg load, 0.03 mg/kg X Crcl q8h, bramycin (Garamycin and q8h; or 5-\0 Ygh1-2ug/mL;or and tre Nebcin 5 mg/kg g24h 60-79:4mg/kgq24 50:3.5mg/kgq24h 40: 2.5 mg/kg g24h <30: Conventional dosing, adjusting trough to <0.5 ug/mL 8 mg/kg load 0.12mg/kg×crdq8h trough 5-10 5 mg/kg daily 60-79:12mg/kgq24h 50: 7.5 mg/kg q24h 40:4.0mg/kgq24h <30: Conventional dosing. justing trough to <5μg/mL Netilmicin mg/kg load, Same as gentamicin and tobramycin 2 mg/kg q8h 50-80:15mg/kgq24-72h Narrow 40:15mg/kgq72-9h 7.5 mg/kg q12h <10:75mg/kgq72-96h 15-25μgmL and trough to 5-10 ug/mL Intravenous preparations (daily cost dollars):$=20-70: $5=71-110: $$=111-150: $$=150-200: SSSS$ 2200. Includes costs of monitoring and tox Table 1.9. Organisms That May Be Susceptible to Aminoglycosides Gentamicin Amikacin Most Enterobacteriaceae Most enterobacteriaceae Most Enterobacteriaceae Yersinia pestis see Figure 1.5) Francisella tularense Francisella tularensis Pseudomonas aeruginosa Mycobacterium avium Brucella spp Brucella spp (combined with doxy (combined with doxycycline) anti-Pseudomonas penicillin cycline) Synergy with penicillins, cephalosporins M tuberculosis mycin, and ceftriaxone for S viridans Synergy with penicillins vancomycin for Enterococ

24 / CHAPTER 1 Table 1.8. Aminoglycosides: Half-Life, Dosing, Renal Dosing, Cost, and Spectrum Antibiotic Half-life Dose Dose for reduced Costa Spectrum (trade name) (h) creatinine clearance (mL/min) Gentamicin 2 2 mg/kg load, 0.03 mg/kg  CrCl q8h, $$$$– Narrow and then adjusting peak to $$$$$ tobramycin 1.7–2 mg/kg 5–10 g/mL (Garamycin and q8h; or and trough 1–2 g/mL; or Nebcin) 5 mg/kg q24h 60–79: 4 mg/kg q24h 50: 3.5 mg/kg q24h 40: 2.5 mg/kg q24h <30: Conventional dosing, adjusting trough to <0.5 g/mL Amikacin 2 8 mg/kg load, 0.12 mg/kg  CrCl q8h, $$$$– Narrow (Amikin) then adjusting peak to $$$$$ 7.5–8 mg/kg 20–40 g/mL, and q8h, or trough 5–10 g/mL, or 15 mg/kg daily 60–79: 12 mg/kg q24h 50: 7.5 mg/kg q24h 40: 4.0 mg/kg q24h <30: Conventional dosing, adjusting trough to <5 g/mL Netilmicin 2.5 2 mg/kg load, Same as gentamicin $$$$– Narrow then and tobramycin $$$$$ 2 mg/kg q8h Streptomycin 2–5 7.5 mg/kg load, 50–80: 15 mg/kg q24–72h $$$$– Narrow then 10–40: 15 mg/kg q72–96h $$$$$ 7.5 mg/kg q12h <10: 7.5 mg/kg q72–96h, adjusting peak to 15–25 g/mL and trough to 5–10 g/mL Intravenous preparations (daily cost dollars): $ = 20–70; $$ = 71–110; $$$ = 111–150; $$$$ = 150–200; $$$$$ ≥ 200. Includes costs of monitoring and toxicity. Table 1.9. Organisms That May Be Susceptible to Aminoglycosides Gentamicin Tobramycin Amikacin Streptomycin Most Enterobacteriaceae Most Enterobacteriaceae Most Enterobacteriaceae Yersinia pestis (see Figure 1.5) (see Figure 1.5) (see Figure 1.5) Francisella tularensis Francisella tularensis Pseudomonas aeruginosa Mycobacterium avium Brucella spp. Brucella spp. (synergy with complex (combined with doxy (combined with doxycycline) anti-Pseudomonas penicillin cycline) Synergy with penicillins, or cephalosporins) M. tuberculosis vancomycin, and ceftriaxone for S. viridans Synergy with penicillins and vancomycin for Enterococcus

ANTI-INFECTIVE THERAPY/ 25 Table 1. 10. Toxicities of miscellaneous antibiotics Clinical symptom Antibiotic 且 Allergic skin ras Steven-Johnson Diarrhea(Clost difficile) Gastrointestinal intolerance Dizziness Neurotoxicity Phlebitis Laboratory tests: Creatinine Cytopenias Eosinophilia AST/ALT个 QT prolonged Glucose↑or↓ Amylase↑ "Red man syn common, but not a true allergic reaction (see text) Gemifloxacin is associated with frequent skin rash in women under 40 years of age. evere and occasionally fatal hepatitis associated with talithromycin Black principle side effect; dark gray less common side effect; light gray = rare side effect; white= not reported or very rare; T= rise; AST/ALT= aspartate aminotransferase/alanine transaminase the concentration of the aminoglycoside that accumu- adjust for renal impairment, the daily dose should be lates in the renal cortex and lowers the incidence of reduced nephrotoxicity. Because aminoglycosides demonstrate Monitoring of serum levels is recommended for concentration-dependent killing, the high peak levels both multidose and once-daily regimens. With multi- achieved with this regimen increase the bactericidal rate dose therapy, blood for a peak level determination and prolong the post-antibiotic effect. In addition, a should be drawn 30 minutes after intravenous infu- once-daily regimen is simpler and less expensive to sion is complete, and for a trough level, 30 minutes administer. This regimen has not been associated with a before the next dose. Blood for peak and trough deter higher incidence of neuromuscular dysfunction. To minations should be drawn after the third dose of

ANTI-INFECTIVE THERAPY / 25 Table 1.10. Toxicities of Miscellaneous Antibiotics Clinical symptom Antibiotic Allergic skin rash a b c Steven–Johnson Diarrhea (Clost. difficile) Gastrointestinal intolerance Hearing loss Dizziness Neurotoxicity Seizure Musculoskeletal Phlebitis Laboratory tests: Coagulation Creatinine↑ Cytopenias Eosinophilia AST/ALT↑ d Bilirubin↑ QT prolonged Glucose↑ or ↓ Amylase↑ a “Red man syndrome” common, but not a true allergic reaction (see text). b Also photosensitivity. c Gemifloxacin is associated with frequent skin rash in women under 40 years of age. d Severe and occasionally fatal hepatitis associated with talithromycin. Black = principle side effect; dark gray  less common side effect; light gray  rare side effect; white  not reported or very rare; ↑  rise; AST/ALT  aspartate aminotransferase/alanine transaminase. Aminoglycosides Vancomycin Macrolides Clindamycin Tetracyclines Chloramphenicol Quinolons Linezolid Quinu/dalfopristin Daptomycin Meronidazole Sulfas the concentration of the aminoglycoside that accumu￾lates in the renal cortex and lowers the incidence of nephrotoxicity. Because aminoglycosides demonstrate concentration-dependent killing, the high peak levels achieved with this regimen increase the bactericidal rate and prolong the post-antibiotic effect. In addition, a once-daily regimen is simpler and less expensive to administer. This regimen has not been associated with a higher incidence of neuromuscular dysfunction. To adjust for renal impairment, the daily dose should be reduced. Monitoring of serum levels is recommended for both multidose and once-daily regimens. With multi￾dose therapy, blood for a peak level determination should be drawn 30 minutes after intravenous infu￾sion is complete, and for a trough level, 30 minutes before the next dose. Blood for peak and trough deter￾minations should be drawn after the third dose of

26/ CHAPTER 1 KEY POINTS advantage of this characteristic. Aminoglycosides also demonstrate persistent suppression of bacterial growth for I to 3 hours after the antibiotic is no longer present About Aminoglycoside Toxicity The higher the concentration of the aminoglycoside the longer the post-antibiotic effect. Aminoglycosides 1. Very low ratio of therapeutic benefit to toxic also demonstrate synergy with antibiotics that act on the cell wall(B-lactam antibiotics and glycopeptides) 2. Monitoring of serum levels usually required The effect of these combinations is greater than the sum of the anti-microbial effects of each individual 3. Nephrotoxicity commonly occurs (usually agent. Synergy has been achieved in the treatment of reversible). Incidence is higher in enterococci,S. viridans, S. aureus, coagulase-negativ a) elderly individuals staphylococci, P aeruginosa, L. monocytogenes, and JK b) patients with pre-existing renal disease, corynebacteria. c) patients with volume depletion and hypoten- An aminoglycoside in combination with other sion, and antibiotics is generally recommended for treatment of d) patients with liver disease the severely ill patients with sepsis syndrome to assure 4. Higher incidence with co-administration of broad coverage for gram-negative bacilli. An amino ancomycin, cephalosporins, clindamycin, pipe- glycoside combined with penicillin is recommende racillin, foscarnet or furosemide r empiric coverage acterial endocarditis 5.The loss of high-frequency hearing and vestibular Tobramycin combined with an anti-pseudomonal dysfunction resulting from ototoxicity is often icillin or an anti-pseudomonal cephalosporin is devastating for elderly individuals. recommended as primary treatment of p aeruginosa. 6. Neuromuscular blockade is rare Streptomycin or gentamicin is the treatment of choice 7. Once-daily therapy may be less toxic. KEY POINTS antibiotic to assure full equilibration within the dis- tribution volume. In the critically ill patient, blood for a peak level determination should be drawn after About Dosing and Serum the first dose to assure achievement of an adequate Monitoring of Aminoglycosides For once-daily do gh levels need to be moni- red to assure adequate clearance. Serum level at 18 hours 1. Aminoglycosides take 15 to 30 minutes to equi- librate in the b should be <l ug/mL. Alternatively, blood for a level deter- mination can be drawn between 6 and 14 hours, and the 2. For multidose therapy, blood for a peak serum level determination should be drawn 30 min- alue applied to a nomogram to help decide on subs utes after infusion quent doses. In the seriously ill patient, blood for a peak level determination should also be drawn 30 minutes after 3. Blood for trough serum level determinations ompletion of the infusion to assure that a therapeutic should be drawn just before the next dose el is being achieved( for gentamicin-tobramycin, a tai 4. Conventionally, aminoglycosides are given get concentration of 16 to 24 ug/mL should be achieved). times daily Dosing should be based on lean Once-daily dosing is not recommended for the treatmen ody weight of enterococcal endocarditis and has not been sufficiently 5. Once-daily dosing takes advantage of studied in pregnancy or in patients with osteomyelitis or ncentration-dependent killing and the post-antibiotic effects of ar 6. Once-daily dosing reduces, but does not elimi- SPECTRUM OF ACTIVITY AND TREATMENT RECOMMENDATIONS 7. In most cases, trough serum levels need to be The aminoglycosides are cidal for most aerobic gram monitored only during once-daily dosing Toxicity egative ding Pseudomonas species. These correlates with high trough levels. agents kill rapidly, and the killing is concentration Ince-daily dosing is not recommended for dependent-that is, the rate increases as the concentra enterococcal endocarditis or pregnant women. tion of the antibiotic increases Once-daily dosing takes

antibiotic to assure full equilibration within the dis￾tribution volume. In the critically ill patient, blood for a peak level determination should be drawn after the first dose to assure achievement of an adequate therapeutic level. For once-daily dosing, trough levels need to be moni￾tored to assure adequate clearance. Serum level at 18 hours should be <1 g/mL. Alternatively, blood for a level deter￾mination can be drawn between 6 and 14 hours, and the value applied to a nomogram to help decide on subse￾quent doses. In the seriously ill patient, blood for a peak level determination should also be drawn 30 minutes after completion of the infusion to assure that a therapeutic level is being achieved (for gentamicin–tobramycin, a tar￾get concentration of 16 to 24 g/mL should be achieved). Once-daily dosing is not recommended for the treatment of enterococcal endocarditis and has not been sufficiently studied in pregnancy or in patients with osteomyelitis or cystic fibrosis. SPECTRUM OF ACTIVITY AND TREATMENT RECOMMENDATIONS The aminoglycosides are cidal for most aerobic gram￾negative bacilli, including Pseudomonas species. These agents kill rapidly, and the killing is concentration￾dependent—that is, the rate increases as the concentra￾tion of the antibiotic increases. Once-daily dosing takes advantage of this characteristic. Aminoglycosides also demonstrate persistent suppression of bacterial growth for 1 to 3 hours after the antibiotic is no longer present. The higher the concentration of the aminoglycoside, the longer the post-antibiotic effect. Aminoglycosides also demonstrate synergy with antibiotics that act on the cell wall (
-lactam antibiotics and glycopeptides). The effect of these combinations is greater than the sum of the anti-microbial effects of each individual agent. Synergy has been achieved in the treatment of enterococci, S. viridans, S. aureus, coagulase-negative staphylococci, P. aeruginosa, L. monocytogenes, and JK corynebacteria. An aminoglycoside in combination with other antibiotics is generally recommended for treatment of the severely ill patients with sepsis syndrome to assure broad coverage for gram-negative bacilli. An amino￾glycoside combined with penicillin is recommended for empiric coverage of bacterial endocarditis. Tobramycin combined with an anti-pseudomonal penicillin or an anti-pseudomonal cephalosporin is recommended as primary treatment of P. aeruginosa. Streptomycin or gentamicin is the treatment of choice for tularemia and Yersinia pestis, and either agent can 26 / CHAPTER 1 1. Very low ratio of therapeutic benefit to toxic side effect. 2. Monitoring of serum levels usually required. 3. Nephrotoxicity commonly occurs (usually reversible). Incidence is higher in a) elderly individuals, b) patients with pre-existing renal disease, c) patients with volume depletion and hypoten￾sion, and d) patients with liver disease. 4. Higher incidence with co-administration of vancomycin, cephalosporins, clindamycin, pipe￾racillin, foscarnet, or furosemide. 5. The loss of high-frequency hearing and vestibular dysfunction resulting from ototoxicity is often devastating for elderly individuals. 6. Neuromuscular blockade is rare. 7. Once-daily therapy may be less toxic. KEY POINTS About Aminoglycoside Toxicity 1. Aminoglycosides take 15 to 30 minutes to equi￾librate in the body. 2. For multidose therapy, blood for a peak serum level determination should be drawn 30 min￾utes after infusion. 3. Blood for trough serum level determinations should be drawn just before the next dose. 4. Conventionally, aminoglycosides are given 3 times daily. Dosing should be based on lean body weight. 5. Once-daily dosing takes advantage of concentration-dependent killing and the post-antibiotic effects of aminoglycosides. 6. Once-daily dosing reduces, but does not elimi￾nate, nephrotoxicity. 7. In most cases, trough serum levels need to be monitored only during once-daily dosing.Toxicity correlates with high trough levels. 8. Once-daily dosing is not recommended for enterococcal endocarditis or pregnant women. KEY POINTS About Dosing and Serum Monitoring of Aminoglycosides

ANTI-INFECTIVE THERAPY/ 27 KEY POINTS KEY POINTS About Aminoglycoside Antibacterial Activity About Glycopeptide Antibacterial Activity 1. 6-Member ring, soluble in water, positively 1. Act on the cell wall of gram-positive bacteria by charged; never with cephalosporins or acidic binding to the D-alanine-D-alanine peptidogly- solutions can precursor 2. Cause temporary holes in bacterial membranes, 2. Require active bacterial growth ind to ribosomal rNa and interfere with trans- 3. Also interfere with RNA synthesis 4. Have a 2-hour post-antibiotic effect 3. Killing is concentration-dependent. 4. The higher the concentration, the longer the post-antibiotic effect. 5. Excellent gram-negative coverage; strepto- cus, and pseudomonas aeruginosa infections. apid infusion is uncommon. Ototoxicity has been reported also be used to treat brucella Gentamicin combined The half-lives of vancomycin (4 to 6 hours) and with penicillin is the treatment of choice for both teicoplanin(40 to 70 hours)are prolonged Table 1.11) S. viridans and Enterococcus faecalis in the anuric patient, the half-life of vancomycin Glycopeptide Antibiotics increases to 7 to 9 days. For vancomycin, peak levels should reach 20 to 50 ug/mL, with trough levels b Table 1. 11, together with Figure 1.5, summarizes the char- maintained at 10 to 12 ug/mL Vancomycin penetrates most tissue spaces, but does not cross the blood-brain barrier in the absence of inflammation. The CHEMISTRY AND MECHANISM OF ACTION cerebrospinal levels are achieved in patients with Vancomycin and teicoplanin are complex glycopeptides meningitis. Unlike vancomycin, which is minimally of approximately 1500 Da molecular weight. These bound to protein, teicoplanin is 90% protein-bound, agents act primarily at the cell wall of gram-positive accounting for its slow renal clearance. Tissue penetra- organisms by binding to the D-alanine-D-alanine tion has not been extensively studied, and little data are precursor and preventing it from being incorporated available on penetration of bone, peritoneal, or cere- into the peptidoglycan. The binding of vancomycin to brospinal fluid his cell wall precursor blocks the transpeptidase and transglycolase enzymes, interfering with cell wall for mation and increasing permeability of the cell. These agents may also interfere with RNA synthesis. The bind rapidly and tightly to bacteria and rapidly kill KEY POINTS actively growing organisms. They also have a 2-hour effect About Vancomycin Toxicity The most common side effect of the glycopeptide. Rapid infusion associated with "red man syn. antibiotics is "red man syndrome, " which occurs mos often when vancomycin is infused rapidly(Table 2. Phlebitis is common 1.10).The patient experiences flushing of the face, 3. Ototoxicity leading to deafness uncommon, neck, and upper thorax. This reaction is thought to be preceeded by tinnitus aused by sudden histamine release secondary to local yperosmolality and not to be a true hypersensitivity reaction. Infusing vancomycin over

also be used to treat Brucella. Gentamicin combined with penicillin is the treatment of choice for both S. viridans and Enterococcus faecalis. Glycopeptide Antibiotics Table 1.11, together with Figure 1.5, summarizes the char￾acteristics of the glycopeptide antibiotics. CHEMISTRY AND MECHANISM OF ACTION Vancomycin and teicoplanin are complex glycopeptides of approximately 1500 Da molecular weight. These agents act primarily at the cell wall of gram-positive organisms by binding to the D-alanine–D-alanine precursor and preventing it from being incorporated into the peptidoglycan. The binding of vancomycin to this cell wall precursor blocks the transpeptidase and transglycolase enzymes, interfering with cell wall for￾mation and increasing permeability of the cell. These agents may also interfere with RNA synthesis. They bind rapidly and tightly to bacteria and rapidly kill actively growing organisms. They also have a 2-hour post-antibiotic effect. TOXICITY The most common side effect of the glycopeptide antibiotics is “red man syndrome,” which occurs most often when vancomycin is infused rapidly (Table 1.10). The patient experiences flushing of the face, neck, and upper thorax. This reaction is thought to be caused by sudden histamine release secondary to local hyperosmolality and not to be a true hypersensitivity reaction. Infusing vancomycin over a 1-hour period usually prevents this reaction. There is less experience with teicoplanin; however, this agent does not cause significant thrombophlebitis, and skin flushing after rapid infusion is uncommon. Ototoxicity has been reported. PHARMACOKINETICS The half-lives of vancomycin (4 to 6 hours) and teicoplanin (40 to 70 hours) are prolonged Table 1.11). Both drugs are excreted primarily by the kidneys, and in the anuric patient, the half-life of vancomycin increases to 7 to 9 days. For vancomycin, peak levels should reach 20 to 50 g/mL, with trough levels being maintained at 10 to 12 g/mL. Vancomycin penetrates most tissue spaces, but does not cross the blood–brain barrier in the absence of inflammation. Therapeutic cerebrospinal levels are achieved in patients with meningitis. Unlike vancomycin, which is minimally bound to protein, teicoplanin is 90% protein-bound, accounting for its slow renal clearance. Tissue penetra￾tion has not been extensively studied, and little data are available on penetration of bone, peritoneal, or cere￾brospinal fluid. ANTI-INFECTIVE THERAPY / 27 1. 6-Member ring, soluble in water, positively charged; never with cephalosporins or acidic solutions. 2. Cause temporary holes in bacterial membranes, bind to ribosomal RNA, and interfere with trans￾lation. 3. Killing is concentration-dependent. 4. The higher the concentration, the longer the post-antibiotic effect. 5. Excellent gram-negative coverage; strepto￾mycin for tularemia and plague. 6. Synergy with penicillins in S. viridans, Enterococ￾cus, and Pseudomonas aeruginosa infections. KEY POINTS About Aminoglycoside Antibacterial Activity 1. Act on the cell wall of gram-positive bacteria by binding to the D-alanine–D-alanine peptidogly￾can precursor. 2. Require active bacterial growth. 3. Also interfere with RNA synthesis. 4. Have a 2-hour post-antibiotic effect. KEY POINTS About Glycopeptide Antibacterial Activity 1. Rapid infusion associated with “red man syn￾drome.” 2. Phlebitis is common. 3. Ototoxicity leading to deafness uncommon, preceeded by tinnitus 4. Rarely nephrotoxic, potentiates aminoglycoside nephrotoxicity KEY POINTS About Vancomycin Toxicity

28/ CHAPTER 1 Table 1.11. Glycopeptides, Macrolides, Clindamycin, Tetracyclines, and Chloramphenicol: Half-Life Dosing, Renal Dosing, Cost, and Spectrum Antibiotic Half-life Dose for reduced Costa (h) creatinine clearance 5mg/kgⅣq12h 40-60:1gq12-24h Narrow (Vancocin (usual dose: 1 g q12h) 20-40: q24-48h 10-20:q48-72h <10q3-7d on levels. trough:10-12μg/mL Teicoplanin 40-70 6 mg/kg IV or IM 10-50: Half the dose Not sold in Narrow <10: One third the dose United States 1. 2-1.6 250-500 mg PO q6h No change required 1gⅣq6h 250-500 mg Po q12h<10:250-500mgq24hs-5 (Biaxin, Biaxin XL) (Zithromax) 10 800 mg PO q24h <30:600mgq24h Narrow Clindamycin 150-300mgPo No change required PO: SSSSs Narrow 300-900mgⅣ Tetracycline 250-500mgPo 50-80:q12h 10-50:q12-24h <10:q24 200 mg PO No change required Minocin, Dynacin twice daily Tigecycline For severe hepatic 50 mg Iv q12h dysfunction 25 mg Iv q12h 025-1gⅣq6h Broad enous preparations( daily cost dollars): $=20-70: $s571-110: SSS =111-150: SSSS=150-200: SSSS$> 200; oral preparations(10- day course cost dollars):5=10-5055=51-100555=101-140:5555=141-180;5552180

28 / CHAPTER 1 Table 1.11. Glycopeptides, Macrolides, Clindamycin, Tetracyclines, and Chloramphenicol: Half-Life, Dosing, Renal Dosing, Cost, and Spectrum Antibiotic Half-life Dose Dose for reduced Costa Spectrum (trade name) (h) creatinine clearance (mL/min) Vancomycin 4–6 15 mg/kg IV q12h 40–60: 1 g q12–24h $ Narrow (Vancocin) (usual dose: 1 g q12h) 20–40: q24–48h 10–20: q48–72h <10: q3–7d Exact dose based on levels: peak: 25–50 g/mL; trough: 10–12 g/mL Teicoplanin 40–70 6 mg/kg IV or IM 10–50: Half the dose Not sold in Narrow (Targocid) followed by <10: One third the dose United 3 mg/kg q24h States Erythromycin 1.2–1.6 250-500 mg PO q6h No change required $ Narrow 1 g IV q6h Clarithromycin 4 250–500 mg PO q12h <10: 250–500 mg q24h $–$$ Narrow (Biaxin, Biaxin XL) XL: 1 g PO q24h Azithromycin 68 500 mg PO, Probably no change $ Narrow (Zithromax) followed by required 250 mg PO q24h, or <10: Not studied 500 mg IV q24h Talithromycin 10 800 mg PO q24h <30: 600 mg q24h $$ Narrow (Ketek) Clindamycin 2.5 150–300 mg PO q6h No change required PO: $$$$$ Narrow (Cleocin) 300–900 mg IV q6–8h IV: $ Tetracycline 8 250–500 mg PO 50–80: q12h $ Broad twice daily 10–50: q12–24h <10: q24h Doxycycline 18 100 mg PO No change required $ Broad (Vibramycin, Doxy) twice daily Minocycline 16 200 mg PO No change required $ Broad (Minocin, Dynacin) twice daily Tigecycline 42 100 mg IV, No change required. $$ Very (Tygecil) followed by For severe hepatic broad 50 mg IV q12h dysfunction, maintenance dose: 25 mg IV q12h Chloramphenicol 4 0.25–1 g IV q6h No change required. $ Broad (Chloromycetin) Serum levels should be monitored in hepatic failure. a Intravenous preparations (daily cost dollars): $ = 20–70; $$ 5 71–110; $$$ = 111–150; $$$$ = 150–200; $$$$$ ≥ 200; oral preparations (10-day course cost dollars): $ = 10–50; $$ = 51–100; $$$ = 101–140; $$$$ = 141–180; $$$$$ ≥ 180