Antibiotic Review & Approach to the Infected Patient. David T. Bearden, Pharm.D. Clinical Associate Professor Pharmacy Practice

Transcription

1 Antibiotic Review & Approach to the Infected Patient David T. Bearden, Pharm.D. Clinical Associate Professor Pharmacy Practice

2 Objectives 1. Categorize antibiotics by their class (and subclass). 2. Identify major pathogens as aerobes/anaerobes and gram positive/negative.

3 Objectives 3. State the coverage of common antibiotics with particular attention to the following: Gram positive Streptococci, Staphylococci, Enterococci Gram negative Enterobacteriaceae, Pseudomonas Anaerobes Bacteroides fragilis

4 Objectives 4. Specify the important side effects and monitoring needs for a given antibiotic. 5. Adopt a thought process for the evaluation of a selected patient and the subsequent selection and monitoring of antibiotic therapy.

5 Why antibiotics? 10 of Top 200 Drugs (5%) 4 Top 100 Drugs (4%) 1 of Top 25 Drugs (4%) Levaquin (#21)

6 Hospitalized

7 Case GZ is a 67 year old male admitted from a long term care facility 4 days ago for surgical repair of a fractured tibia. After successful surgery, but failure to be removed from the ventilator, GZ develops a fever with increased production of respiratory secretions. Blood and endotracheal aspirate cultures are collected and a chest X-ray is obtained.

8 Medical History Allergies: SH: PMH: NKDA TOB, EtOH, IVDA Type 2 Diabetes Hypertension

9 Current Medications Current meds: Insulin drip 1 U/hour Morphine drip 2mg/hour Enalapril 1.25 mg IV q6h Cimetidine 300 mg IV q8h Enoxaparin 30 mg SQ q12h

10 Vitals, Labs, Ht & Wt Temp: F RR: 20 (per ventilator) HR: 122 BP: 126/74 Labs: BUN 18 SCr 0.8 WBC 14.2; 10% B, 69% N, 20% L, 10% M Wt: 84 kg Ht: 180 cm

11 General Questions What are GZ s signs and symptoms of infection? How severe is GZ s condition? For which pathogens is GZ at most risk?

12 Empiric Therapy GZ s respiratory status continues to deteriorate. The chest x-ray shows an infiltrate in the RLL. Endotracheal suction gram stain shows gram negative rods. What empiric treatment would you recommend?

13 Monitoring After 24 hours GZ is not improved, and continues with his current level of cardiovascular and ventilatory support. The preliminary culture results are gram negative rods, with confirmation pending. What therapy changes should be recommended?

14 Monitoring: Clinical & Culture Results After 48 hours GZ is worsening and requires increasing amounts of respiratory support and now requires circulatory support with vasopressors (dopamine is started; enalapril has been discontinued). Culture results report growth of Klebsiella pneumoniae with sensitivities. What changes in therapy would you recommend?

15 Monitoring: Clinical 48 hours after the antibiotic changes above, GZ s temperature and WBC begin to normalize. Pulmonary secretions are decreasing. The chest X-ray however, shows no change. Should therapy be altered?

16 Monitoring: Duration of Therapy Over the next ten days GZ continues to improve, and is weaned from the ventilator. For how long should you recommend antibiotic continuance?

17 Why know the bugs?

18 Why know the diseases?

19 Microbiology 101

20 Major Pathogen Groups Bacteria Fungi Viruses Parasites

21 General Bacterial Classifications Oxygen required? Aerobe Anaerobe Gram Stain Gram Positive Gram Negative

22 GPC GPC GPC GPC GPC GPC Shapes GPC GPC GPC GPC GPC GPC GPC GPC GPC GPC GPC GPC GNR GNR GNR

23 Important Bacteria: Aerobic Gram Positive Cocci Staphylococci S. aureus Coag-negative Staph Streptococci S. pneumoniae Group B Stept Viridans Strept Enterococci E. faecalis E. faecium

24 Important Bacteria: Aerobic Gram Negatives Gram negative rods E. coli K. pneumoniae Serratia, Enterobacter H. influenzae P. aeruginosa Gram negative cocci M. catarrhalis N. gonorrhoeae N. meningitidis

25 Important Bacteria: Atypical Respiratory Aerobes Atypicals Legionella sp Mycoplasma pneumoniae Chlamydia pneumoniae

26 Important Bacteria: Anaerobes True Anaerobes (Think gut!) Bacteroides fragilis Clostridium difficile (diarrhea) Oral Anaerobes Prevotella Peptostreptococcus

27 Things to Know About Class & Subclass Mechanism of action Coverage Side Effects Dosage issues Special monitoring

28 Class & Subclass β-lactams Penicillins Natural Amino- Penicillinase R Extended Spectrum Inhibitor combo Cephalosporins 1 st, 2 nd, 3 rd, 4 th Carbapenems Monobactams Aminoglycosides Fluoroquinolones Macrolides Anti-anaerobes Gram positive drugs Glycopeptides Oxazolidinones Streptogramins Sulfa drugs Tetracyclines

29 Gram Positives Gram Negatives Anaerobes B. fragilis Oral anaerobes Pseudomonas H. flu Kleb E.coli Enterococcus MRSA MSSA Strep

30 Which Chart?? Condensed chart Need to know: + Reasonable choice for coverage +/- Variable activity (Resistance) - Should not be used to treat ++ Excellent activity

31 Acronym Game - MRSA Methicillin Resistant Staphylococcus aureus Methicillin resistant also means. Penicillin resistant Cephalosporin resistant Mostly β-lactam resistant Drug of choice Vancomycin MSSA : methicillin-sensitive S. aureus

32 Penicillins MOA & Resistance MOA-β-lactam, inhibit cell wall synthesis Resistance β-lactamases Altered PBPs

33 Natural Penicillin Very specific uses, often resistant Gram positive - Streptococci Gram negative - None Anaerobes - Oral only Others Drug of Choice: N. meningitidis, syphilis

34 Aminopenicillins Ampicillin, amoxicillin Respiratory infections, often resistance Gram positive Strept, Enterococci Gram negative some Anaerobes Oral only

35 Penicillinase-resistant penicillins Penicillinase resistant dicloxacillin, nafcillin Major use: drug of choice for MSSA Gram positive Strept, MSSA Gram negative none Anaerobes Oral only

36 Extended-Spectrum Penicillins Extended-spectrum piperacillin, ticarcillin Broad spectrum, severe infections Gram positive Strept, Staph,?Enterococci Gram negative excellent, include P. aerug Anaerobes Oral, some true

37 Penicillin / β-lactamase inhibitor β-lactamase inhibitor MSSA & Enterobacteriaceae & anaerobes Will not add non-existent coverage Gram positive Strept, MSSA,?Enterococci Gram negative excellent,?p. aeruginosa Anaerobes Excellent all

38 Gram Positives Gram Negatives Anaerobe B. fragilis Oral Pseudo H. flu Kleb E.coli Entero MRSA MSSA Strep Penicillin /- +/ /- +/ / / Ampicillin Am/sulbactam Amoxicillin Amox/clav Dicloxacillin Nafcillin Piperacillin Pip/tazo

39 Penicillins adverse reactions Common Allergic reactions Anaphlyaxis, rash, urticaria, fever Diarrhea 5-20% patients report allergy 4-15/100,000 courses anaphylaxis 2-3% rashes

40 Penicillins adverse reactions Less common Hematologic anemia, thrombocytopenia Hepatitis/biliary nafcillin/oxacillin Interstitial nephritis nafcillin/oxacillin Seizures high doses

41 Penicillins dosing / monitoring Mostly renally cleared Adjust for renal function changes Exceptions Nafcillin, oxacillin, dicloxacillin Biliary excretion, no renal adjustments Toxicity monitoring

42 Cephalosporins MOA & Resistance MOA-β-lactam, inhibit cell wall synthesis Resistance β-lactamases Altered PBPs

43 Cephalosporin Generations

44 Cephalosporin Generations Cefazolin & Cephalexin Cefuroxime & Cefoxitin Ceftriaxone & Ceftazidime Cefepime

45 Cephalosporins NOT COVERED EVER!!

46 1 st Generation Cephalosporins Cefazolin, cephalexin Good for skin infections, some respiratory Gram positive Strept, MSSA Gram negative some E.coli, Kleb Anaerobes Oral only

47 2 nd Generation Cephalosporins Cefuroxime, cefotetan, cefoxitin Some respiratory (oral), [GI infections] Gram positive Strept, MSSA Gram negative good coverage Anaerobes Oral Cefoxitin/cefotetan B. fragilis

48 3 rd Generation Cephalosporins Ceftriaxone, cefotaxime, ceftazidime Respiratory infections, serious infections Gram positive ~Strept, ~MSSA Gram negative Very good Ceftazidime P. aeruginosa Anaerobes - Oral only

49 4 th Generation Cephalosporins Cefepime Serious hospital infections Gram positive Strept, MSSA Gram negative Excellent, P. aeruginosa Anaerobes - Oral only

50 Gram Positives Gram Negatives Anaerobe Cefazolin Cephalexin Cefuroxime Cefoxitin Ceftriaxone Ceftazidime Cefepime Pseudo H. flu Kleb E.coli Entero MRSA MSSA Strep Oral / / / B. fragilis +

51 Cephalosporins adverse reactions Common Allergic reactions Anaphlyaxis, rash, urticaria, fever 3-7% cross resistance with PCN allergy Diarrhea

52 Oral Cephalosporins First Generation Cephalexin (Keflex) Cephadrine (Velosef) Cefadroxil (Duricef) Second Generation Cefaclor (Ceclor) Cefprozil (Cefzil) Cefuroxime (Ceftin) Loracarbef (Lorabid) Third Generation Cefixime (Suprax) Cefpodoxime (Vantin) Ceftibuten (Cedax) Cefdinavir (Omnicef) Cefditoren (Spectracef) Divided by generations Little difference in spectrum due to concentrations Variable MICs and pharmacokinetics

53 Cephalosporins adverse reactions Less common Hematologic anemia, thrombocytopenia Seizures high doses

54 Cephalosporins dosing / monitoring Mostly renally cleared Adjust for renal function changes Exceptions Ceftriaxone Biliary excretion, no renal adjustment Toxicity monitoring

55 Carbapenems / Monobactams MOA & Resistance MOA ~ β-lactam, inhibit cell wall synthesis Resistance β-lactamases Outer membrane protein mutations - carbapenems

56 Carbapenems Imipenem, meropenem, ertapenem Very broad spectrum, severe infections Gram positive Strept, MSSA Gram negative majority, P. aerug ( erta) Anaerobes - Excellent

57 Monobactams Aztreonam No PCN allergy cross reactivity Gram positive None Gram negative most, P.aeruginosa Anaerobes - None

58 Gram Positives Gram Negatives Anaerobe B. fragilis Oral Pseudo H. flu Kleb E.coli Entero MRSA MSSA Strep Imipenem Aztreonam + + +/

59 Carbapenems / Monobactams adverse reactions Common Gastrointestinal

60 Carbapenems / Monobactams adverse reactions Less common Allergic reactions carbapenems Avoid with severe PCN allergies Hematologic anemia, thrombocytopenia Seizures carbapenems High doses Predisposing factors

61 Carbapenems / Monobactams dosing / monitoring Renally cleared Adjust for renal function changes Toxicity monitoring

62 β-lactam Summary Penicillins mild, moderate, severe Cephalosporins mild, moderate, severe Carbapenems severe Monobactams severe Well tolerated allergic potentials

63 Aminoglycosides MOA & Resistance MOA ribosomal protein synthesis inhibitor Resistance Inactivating enzymes

64 Aminoglycosides Gentamicin, tobramycin, amikacin Good gram (-) activity, severe infections Gram positive only synergistic Gram negative majority, P. aerug Anaerobes none

65 Gram Positives Gram Negatives Anaerobe Tobramycin Amikacin Pseudo H. flu Kleb E.coli Entero MRSA MSSA Strep Gentamicin Oral B. fragilis * Can be used w/other abx for synergy versus Gram (+)

66 Aminoglycosides adverse reactions Common Nephrotoxicity 10-15% incidence, often within 5-7 days Usually reversible Ototoxicity 1-5% incidence, cochlear & vestibular Often irreversible

67 Aminoglycosides adverse reactions Less common Neuromuscular paralysis Large, rapid doses Myasthenia gravis

68 Aminoglycosides dosing Dosage according to: Weight Renal function Severity / site of infection

69 Aminoglycosides monitoring Drug concentrations Correlate with efficacy and toxicity Renal function Monitor for signs of toxicity BUN / Serum creatinine urine output

70 Fluoroquinolones MOA & Resistance MOA Inhibit DNA synthesis via DNA gyrase and topoisomerase IV Resistance Mutations at target sites (gyrase, topo IV) Efflux pumps that pump drugs out of bacteria

71 Fluoroquinolones Ciprofloxacin, levo-, moxi-, gemi- Potent agents, most gram (-), some gram (+) Gram positive Strept, MSSA (cipro poor) Gram negative majority, P. aerug Anaerobes variable, minimal Atypical respiratory pathogens Legionella sp, Chlamydia pneumoniae, Mycoplasma pneumoniae

72 Gram Positives Gram Negatives Anaerobe Ciprofloxacin Levofloxacin Moxifloxacin Pseudo H. flu Kleb E.coli Entero MRSA MSSA Strep Oral B. fragilis +/ / / /- +/- +/- PLUS Atypicals: Legionella, C. pneumoniae, M. pneumoniae

73 Fluoroquinolones adverse reactions Common Gastrointestinal Nausea Central nervous system HA, dizziness, insomnia

74 Fluoroquinolones adverse reactions Less common Cartilage toxicity: AVOID children/pregnancy CNS: confusion, seizures Prolonged cardiac QT interval Increased with other similar drugs

75 Fluoroquinolones dosing / monitoring Most adjusted for renal function Drug interactions Oral binding with cations Calcium, iron, antacids, enteral feeding Equal oral & IV bioavailability Monitor for toxicity

76 Macrolides MOA & Resistance MOA ribosomal protein synthesis inhibitor Resistance Mutations at ribosomal target sites Efflux pumps that pump drugs out of bacteria

77 Macrolides Erythromycin, clarithromycin, azithromycin Good coverage of respiratory infections Gram positive Strept, ~MSSA Gram negative minimal (H. flu) Anaerobes oral only Atypical respiratory pathogens Legionella sp, Chlamydia pneumoniae, Mycoplasma pneumoniae

78 Gram Positives Gram Negatives Anaerobe B. fragilis Oral Pseudo H. flu Kleb E.coli Entero MRSA MSSA Strep Erythromycin +/- Clarithromycin /- + + PLUS Atypicals: Legionella, C. pneumoniae, M. pneumoniae

79 Macrolides adverse reactions Common Gastrointestinal Nausea, vomiting, diarrhea Erythro > clarithro > azithro Phlebitis IV erythromycin

80 Macrolides adverse reactions Less common Prolonged cardiac QT interval Increased with other similar drugs Erythro > clarithro >> azithro

81 Macrolides dosing / monitoring Adjusted for renal function Multiple drug interactions Inhibit liver CYP450-3A4 Erythro >> clarithro >> azithro Monitor for toxicity

82 MOA Anti-Anaerobes MOA & Resistance Metronidazole: free radicals Clindamycin: ribosomal protein synthesis inhibitor Resistance Metronidazole: rare Clindamycin: mutations in ribosomes

83 Metronidazole Only anaerobes! Gram positive none Gram negative none Anaerobes excellent

84 Clindamycin Gram positives and anaerobes Gram positive Strept, MSSA Gram negative none Anaerobes good coverage (o.k. B. fragilis)

85 Gram Positives Gram Negatives Anaerobe B. fragilis Oral Pseudo H. flu Kleb E.coli Entero MRSA MSSA Strep Clindamycin Metronidazole + ++

86 Clindamycin adverse reactions Common Gastrointestinal Diarrhea Clostridium difficile

87 Common Metronidazole adverse reactions Nausea Metallic taste Drug interaction Disulfiram reaction Flushing, sweating, nausea with alcohol Can persist few days after metronidazole

88 Anti-Anaerobes dosing / monitoring Neither adjusted for renal function Both equally bioavailable IV and oral Monitor for toxicity

89 Gram Positive Drugs MOA & Resistance MOA Vancomycin: inhibits cell wall synthesis Linezolid: ribosomal protein synthesis inhibitor Quinupristin/dalfopristin: ribosomes Daptomycin: cell membrane leaks Resistance Vancomycin: altered cell walls Quinupristin/dalfopristin & Linezolid Rare mutations of ribosomes

90 Vancomycin Gram positive only, DOC for MRSA Gram positive Strept, all Staph, ~Entero Gram negative none Anaerobes gram positive oral only

91 Linezolid Gram positives only, serious infections Gram positive Strept, all Staph, Entero Gram negative none (~H.flu) Anaerobes none Drug of choice for: Vancomycin-resistant Enterococcus (VRE)

92 Daptomycin Gram positives only, serious infections Gram positive Strept, all Staph, all Entero Gram negative none Anaerobes none

93 Gram Positives Gram Negatives Anaerobe B. fragilis Oral Pseudo H. flu Kleb E.coli Entero MRSA MSSA Strep Linezolid Vancomycin /

94 Gram Positive Drugs adverse reactions Vancomycin Red-man syndrome: infusion related flushing Nephrotoxocity with other agents Ototoxicity with high concentrations Linezolid Thrombocytopenia, anemia, neutropenia Daptomycin Skeletal muscle

95 Vancomycin dosing / monitoring Weight and renal function based dosing Oral formulation no systemic concentration Monitoring Serum concentrations (controversy) Renal function with other nephrotoxins

96 Gram Positive Drugs dosing / monitoring Linezolid Monoamine oxidase inhibitor Equal bioavailability oral and IV Monitor complete blood counts Daptomycin Weight based

97 Sulfa Drugs/Tetracyclines MOA MOA & Resistance Sulfa & trimethoprim: inhibits folic acid synthesis via enzyme inhibition Tetracyclines: ribosomal protein synthesis inhibitor Resistance Sulfas alterations in target enzymes Tetracyclines efflux pumps

98 Trimethoprim/sulfamethoxazole Variable wide activity Gram positive Strept, MSSA Gram negative most Enterobacteriacae Anaerobes oral only

99 Tetracyclines (tetra-, doxy-, mino-) Respiratory, intracellular infections Gram positive Strept, MSSA Gram negative H. flu Anaerobes Mostly oral Atypical respiratory pathogens Legionella sp, Chlamydia pneumoniae, Mycoplasma pneumoniae

100 Tigecycline Glycylcycline tetracycline derivative Broad spectrum Gram positives: MRSA, VRE Gram negatives: enterobacteriaceae, Acinetobacter True anaerobes Atypicals Primarily GI Side effects Approved in 2005, still reserved for severe resistant infections

101 Gram Positives Gram Negatives Anaerobe B. fragilis Oral Pseudo H. flu Kleb E.coli Entero MRSA MSSA Strep TMP/SMX + + +/

102 Sulfa Drugs/Tetracyclines adverse reactions TMP/SMX Allergic reactions rash, fever GI effects Neutropenia, thrombocytopenia Tetracyclines Photosensitivity Nausea and diarrhea Tooth discoloration (children)

103 Sulfa Drugs/Tetracyclines dosing / monitoring TMP/SMX Increases effects of warfarin Tetracyclines Chelate with cations/calcium/dairy products Separate administration Monitoring for toxicity

104 Drugs that cover Pseudomonas Aminoglycosides Fluoroquinolones Ceftazidime, cefepime Piperacillin, ticarcillin Aztreonam Imipenem, meropenem

105 Drugs that cover MRSA Vancomycin Linezolid Daptomycin Tigecycline

106 True Anaerobic Coverage Piperacillin β-lactam/β-lactamase inhibitors Cefoxitin Imipenem, meropenem Metronidazole Clindamycin

107 Plus, minus, plus plus?? In general Know + or +/- is less important Safe side: consider a minus

108

109 How to approach an infected patient

110 General Approach 1. Infected? 2. Likely pathogens? 3. Which initial (empiric) antibiotic? 4. Now what?

111 Case: Highlights 67 y/o male From Long Term Care Facility Broken leg 4 days ago surgery Stays on ventilator after surgery Fever, respiratory secretions

112 Fever Elderly may be afebrile Low temperature/shock Drugs may mask Steroids Anti-pyretics APAP ASA NSAIDS

113 Peripheral White Blood Count Normal WBC ,000 / mm 3 Infected WBC > 10,000 / mm 3

114 Normal Peripheral WBC s

115 Left Shift

116 Intuitive Signs & Symptoms Pain Inflammation NOT absolute

117 Laboratory Tests WBC and/or pathogens (in sterile sites) Spinal fluid Blood Joint fluid

118 Severity of Illness Abnormal VS Organ system dysfunctions

119 Case 1. Fever F 2. WBC w/ left shift 3. Inflammation? Chest X-ray Pending 4. WBC/pathogens? Pending 5. Overall status Abnormal VS Organ dysfunction Lung (ventilator)

120 Infection Site Extremely important Often sole criteria for possible pathogens Examples Skin : Staph & Strep CAP : S. pneumoniae, H. flu, atypicals UTI: E. coli

121 Pathogen Risks Age Immune status Location Concomitant diseases Concomitant drugs

122 Case: Risks Chronic illness related Advanced age Diabetes Acute illness related Ventilator Surgery Drug related H2-blocker Morphine?

123 Case: Suspected pathogens Core pathogens Enterobacteriaceae H. flu, S. pneumoniae S. aureus* Pseudomonas Acinetobacter

124 Any other lab tests? Gram stains? Rapid Limited information Interpretation Preliminary culture results? Very helpful Often delayed Interpretation

125 General Approach 1. Infected? YES 2. Likely pathogens? Gram (-) enterics, Pseudomonas, S. pneumoniae, MSSA 3. Which initial antibiotic? 4. Now what?

126 Worsening Clinically deteriorating Increased ventilator support Fever increased, BP worsened Chest X-ray is worsening Culture results gram stain Gram (-) rods

127 Host Factors Allergies Age elimination Pregnancy kinetics, toxicity Renal & hepatic function Other drugs interactions, overlap toxicity Disease states kinetics, toxicity, efficacy Immune status potent agents?

128 Drug Factors Spectrum General ever cover likely bugs Specific local, state, region sensitivities Site penetration CNS (Blood Brain Barrier) Lung?

129 Drug Factors Toxicity Ease of administration Oral Doses per day IV compatibility

130 Drug Factors Cost Drugs IV lines Monitoring (labs) Resistance costs

131 Combination Therapy Broaden coverage Synergy Preventing resistance Disadvantages

132 Multiple Drugs Combination Therapy Broaden coverage Ceftazidime plus metronidazole Gram (-) s + Anaerobes Cefepime plus vancomycin Gram (-) s + Gram (+) s

133 Bugs to Double Cover erratia seudomonas cinetobacter itrobacter nterobacter

134 Combination Therapy When does

135 Can you say

136 Synergy

137 Synergy

138 Synergy

139 Combination Therapy Negatives Toxicity of 2 drugs Antagonism

140 Case: what treatment to begin? Host Allergy None Age 67, renal o.k. Other meds no toxic Dz states no change Immune normal Drugs Spectrum wide Lung penetration? Toxicity know Administration no Costs similar Combination yes

141 Case: Antibiotic choices Bugs to cover? Gram stain GNR Worst case is Pseudomonas Which drug(s) are best for Pseudomonas?

142 Case: What treatment to begin? Suggestions Aminoglycoside or fluoroquinolone plus Ceftazidime or cefepime Piperacillin Imipenem Aztreonam

143 Empiric decision Gentamicin 500 mg IV q24h Ceftazidime 2g IV q8h Await culture results

144 Case: monitoring After 24 hours of abx Stable, not cured Culture GNR Any changes??

145 Culture interpretation Growth Colonization, contamination, infection? No growth No infection? Antibiotics limit cultures Organisms difficult to grow Transient organisms

146 Pathogen ID Time-Line Gentamicin - Sensitive Ceftriaxone - Resistant DAY 1: Culture taken Preliminary Gram stain DAY 1-2: Culture bottle +, Gram stain Culture plated DAY 2-3: Preliminary ID Final ID DAY 3-4: Sensitivities

147 Antibiotic Time-Line DAY 1: Culture taken Preliminary Gram stain DAY 1-2: Culture bottle +, Gram stain Culture plated DAY 2-3: Preliminary ID Final ID Empiric Therapy Most likely pathogens (Broad coverage) Change therapy? - use available info! Change therapy? - use available info! Gentamicin - Sensitive Ceftriaxone - Resistant DAY 3-4: Sensitivities Change therapy? - narrow spectrum

148 Case Continue therapy Stable patient Coverage of GNR reasonable Awaiting organism & antibiotic sensitivities

149 Case: 48 hours worsens + cultures Klebsiella pneumoniae Resistant ceftaz, ceftriaxone, piperacillin, gentamicin Intermediate levofloxacin Sensitive imipenem, amikacin Change to: Imipenem 500 mg IV q6h Amikacin 2g IV q24h

150 Improvement Fever WBC Clinical symptoms Radiologic may be slow

151 Route of administration Current IV drug available orally? Similar oral drug available? Criteria for oral therapy: Clinically stable/improving Afebrile hours WBC GI tract O.K.

152 Case No oral forms Amikacin Imipenem No suitable oral alternatives Continual monitoring for side effects

153 Length of Therapy Very little data Often conventional 10 days, 14 days, 21 days Patient specific Severity Site of infection Speed of improvement Immune status

154 Case: Duration of therapy Individualized to patient 14 days if responding quickly Can increase to 21 days if needed