Antibiotic Review & Approach to the Infected Patient David T. Bearden, Pharm.D. Clinical Associate Professor Pharmacy Practice
Objectives 1. Categorize antibiotics by their class (and subclass). 2. Identify major pathogens as aerobes/anaerobes and gram positive/negative.
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
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.
Why antibiotics? 10 of Top 200 Drugs (5%) 4 Top 100 Drugs (4%) 1 of Top 25 Drugs (4%) Levaquin (#21) 2006 www.rxlist.com
Hospitalized
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.
Medical History Allergies: SH: PMH: NKDA TOB, EtOH, IVDA Type 2 Diabetes Hypertension
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
Vitals, Labs, Ht & Wt Temp: 102.1 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
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?
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?
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?
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?
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?
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?
Why know the bugs?
Why know the diseases?
Microbiology 101
Major Pathogen Groups Bacteria Fungi Viruses Parasites
General Bacterial Classifications Oxygen required? Aerobe Anaerobe Gram Stain Gram Positive Gram Negative
GPC GPC GPC GPC GPC GPC Shapes GPC GPC GPC GPC GPC GPC GPC GPC GPC GPC GPC GPC GNR GNR GNR
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
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
Important Bacteria: Atypical Respiratory Aerobes Atypicals Legionella sp Mycoplasma pneumoniae Chlamydia pneumoniae
Important Bacteria: Anaerobes True Anaerobes (Think gut!) Bacteroides fragilis Clostridium difficile (diarrhea) Oral Anaerobes Prevotella Peptostreptococcus
Things to Know About Class & Subclass Mechanism of action Coverage Side Effects Dosage issues Special monitoring
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
Gram Positives Gram Negatives Anaerobes B. fragilis Oral anaerobes Pseudomonas H. flu Kleb E.coli Enterococcus MRSA MSSA Strep
Which Chart?? Condensed chart Need to know: + Reasonable choice for coverage +/- Variable activity (Resistance) - Should not be used to treat ++ Excellent activity
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
Penicillins MOA & Resistance MOA-β-lactam, inhibit cell wall synthesis Resistance β-lactamases Altered PBPs
Natural Penicillin Very specific uses, often resistant Gram positive - Streptococci Gram negative - None Anaerobes - Oral only Others Drug of Choice: N. meningitidis, syphilis
Aminopenicillins Ampicillin, amoxicillin Respiratory infections, often resistance Gram positive Strept, Enterococci Gram negative some Anaerobes Oral only
Penicillinase-resistant penicillins Penicillinase resistant dicloxacillin, nafcillin Major use: drug of choice for MSSA Gram positive Strept, MSSA Gram negative none Anaerobes Oral only
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
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
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
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
Penicillins adverse reactions Less common Hematologic anemia, thrombocytopenia Hepatitis/biliary nafcillin/oxacillin Interstitial nephritis nafcillin/oxacillin Seizures high doses
Penicillins dosing / monitoring Mostly renally cleared Adjust for renal function changes Exceptions Nafcillin, oxacillin, dicloxacillin Biliary excretion, no renal adjustments Toxicity monitoring
Cephalosporins MOA & Resistance MOA-β-lactam, inhibit cell wall synthesis Resistance β-lactamases Altered PBPs
Cephalosporin Generations +++ - ++ -- + --- +++ ---
Cephalosporin Generations Cefazolin & Cephalexin Cefuroxime & Cefoxitin Ceftriaxone & Ceftazidime Cefepime
Cephalosporins NOT COVERED EVER!!
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
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
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
4 th Generation Cephalosporins Cefepime Serious hospital infections Gram positive Strept, MSSA Gram negative Excellent, P. aeruginosa Anaerobes - Oral only
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 +
Cephalosporins adverse reactions Common Allergic reactions Anaphlyaxis, rash, urticaria, fever 3-7% cross resistance with PCN allergy Diarrhea
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
Cephalosporins adverse reactions Less common Hematologic anemia, thrombocytopenia Seizures high doses
Cephalosporins dosing / monitoring Mostly renally cleared Adjust for renal function changes Exceptions Ceftriaxone Biliary excretion, no renal adjustment Toxicity monitoring
Carbapenems / Monobactams MOA & Resistance MOA ~ β-lactam, inhibit cell wall synthesis Resistance β-lactamases Outer membrane protein mutations - carbapenems
Carbapenems Imipenem, meropenem, ertapenem Very broad spectrum, severe infections Gram positive Strept, MSSA Gram negative majority, P. aerug ( erta) Anaerobes - Excellent
Monobactams Aztreonam No PCN allergy cross reactivity Gram positive None Gram negative most, P.aeruginosa Anaerobes - None
Gram Positives Gram Negatives Anaerobe B. fragilis Oral Pseudo H. flu Kleb E.coli Entero MRSA MSSA Strep Imipenem Aztreonam + + +/- + + + + + ++ + + + +
Carbapenems / Monobactams adverse reactions Common Gastrointestinal
Carbapenems / Monobactams adverse reactions Less common Allergic reactions carbapenems Avoid with severe PCN allergies Hematologic anemia, thrombocytopenia Seizures carbapenems High doses Predisposing factors
Carbapenems / Monobactams dosing / monitoring Renally cleared Adjust for renal function changes Toxicity monitoring
β-lactam Summary Penicillins mild, moderate, severe Cephalosporins mild, moderate, severe Carbapenems severe Monobactams severe Well tolerated allergic potentials
Aminoglycosides MOA & Resistance MOA ribosomal protein synthesis inhibitor Resistance Inactivating enzymes
Aminoglycosides Gentamicin, tobramycin, amikacin Good gram (-) activity, severe infections Gram positive only synergistic Gram negative majority, P. aerug Anaerobes none
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 (+)
Aminoglycosides adverse reactions Common Nephrotoxicity 10-15% incidence, often within 5-7 days Usually reversible Ototoxicity 1-5% incidence, cochlear & vestibular Often irreversible
Aminoglycosides adverse reactions Less common Neuromuscular paralysis Large, rapid doses Myasthenia gravis
Aminoglycosides dosing Dosage according to: Weight Renal function Severity / site of infection
Aminoglycosides monitoring Drug concentrations Correlate with efficacy and toxicity Renal function Monitor for signs of toxicity BUN / Serum creatinine urine output
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
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
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
Fluoroquinolones adverse reactions Common Gastrointestinal Nausea Central nervous system HA, dizziness, insomnia
Fluoroquinolones adverse reactions Less common Cartilage toxicity: AVOID children/pregnancy CNS: confusion, seizures Prolonged cardiac QT interval Increased with other similar drugs
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
Macrolides MOA & Resistance MOA ribosomal protein synthesis inhibitor Resistance Mutations at ribosomal target sites Efflux pumps that pump drugs out of bacteria
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
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
Macrolides adverse reactions Common Gastrointestinal Nausea, vomiting, diarrhea Erythro > clarithro > azithro Phlebitis IV erythromycin
Macrolides adverse reactions Less common Prolonged cardiac QT interval Increased with other similar drugs Erythro > clarithro >> azithro
Macrolides dosing / monitoring Adjusted for renal function Multiple drug interactions Inhibit liver CYP450-3A4 Erythro >> clarithro >> azithro Monitor for toxicity
MOA Anti-Anaerobes MOA & Resistance Metronidazole: free radicals Clindamycin: ribosomal protein synthesis inhibitor Resistance Metronidazole: rare Clindamycin: mutations in ribosomes
Metronidazole Only anaerobes! Gram positive none Gram negative none Anaerobes excellent
Clindamycin Gram positives and anaerobes Gram positive Strept, MSSA Gram negative none Anaerobes good coverage (o.k. B. fragilis)
Gram Positives Gram Negatives Anaerobe B. fragilis Oral Pseudo H. flu Kleb E.coli Entero MRSA MSSA Strep Clindamycin + + + + Metronidazole + ++
Clindamycin adverse reactions Common Gastrointestinal Diarrhea Clostridium difficile
Common Metronidazole adverse reactions Nausea Metallic taste Drug interaction Disulfiram reaction Flushing, sweating, nausea with alcohol Can persist few days after metronidazole
Anti-Anaerobes dosing / monitoring Neither adjusted for renal function Both equally bioavailable IV and oral Monitor for toxicity
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
Vancomycin Gram positive only, DOC for MRSA Gram positive Strept, all Staph, ~Entero Gram negative none Anaerobes gram positive oral only
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)
Daptomycin Gram positives only, serious infections Gram positive Strept, all Staph, all Entero Gram negative none Anaerobes none
Gram Positives Gram Negatives Anaerobe B. fragilis Oral Pseudo H. flu Kleb E.coli Entero MRSA MSSA Strep Linezolid Vancomycin ++ ++ ++ ++ +/- ++ ++ ++ + +
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
Vancomycin dosing / monitoring Weight and renal function based dosing Oral formulation no systemic concentration Monitoring Serum concentrations (controversy) Renal function with other nephrotoxins
Gram Positive Drugs dosing / monitoring Linezolid Monoamine oxidase inhibitor Equal bioavailability oral and IV Monitor complete blood counts Daptomycin Weight based
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
Trimethoprim/sulfamethoxazole Variable wide activity Gram positive Strept, MSSA Gram negative most Enterobacteriacae Anaerobes oral only
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
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
Gram Positives Gram Negatives Anaerobe B. fragilis Oral Pseudo H. flu Kleb E.coli Entero MRSA MSSA Strep TMP/SMX + + +/- + + + +
Sulfa Drugs/Tetracyclines adverse reactions TMP/SMX Allergic reactions rash, fever GI effects Neutropenia, thrombocytopenia Tetracyclines Photosensitivity Nausea and diarrhea Tooth discoloration (children)
Sulfa Drugs/Tetracyclines dosing / monitoring TMP/SMX Increases effects of warfarin Tetracyclines Chelate with cations/calcium/dairy products Separate administration Monitoring for toxicity
Drugs that cover Pseudomonas Aminoglycosides Fluoroquinolones Ceftazidime, cefepime Piperacillin, ticarcillin Aztreonam Imipenem, meropenem
Drugs that cover MRSA Vancomycin Linezolid Daptomycin Tigecycline
True Anaerobic Coverage Piperacillin β-lactam/β-lactamase inhibitors Cefoxitin Imipenem, meropenem Metronidazole Clindamycin
Plus, minus, plus plus?? In general Know + or +/- is less important Safe side: consider a minus
How to approach an infected patient
General Approach 1. Infected? 2. Likely pathogens? 3. Which initial (empiric) antibiotic? 4. Now what?
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
Fever Elderly may be afebrile Low temperature/shock Drugs may mask Steroids Anti-pyretics APAP ASA NSAIDS
Peripheral White Blood Count Normal WBC 4000 10,000 / mm 3 Infected WBC > 10,000 / mm 3
Normal Peripheral WBC s
Left Shift
Intuitive Signs & Symptoms Pain Inflammation NOT absolute
Laboratory Tests WBC and/or pathogens (in sterile sites) Spinal fluid Blood Joint fluid
Severity of Illness Abnormal VS Organ system dysfunctions
Case 1. Fever 102.1 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)
Infection Site Extremely important Often sole criteria for possible pathogens Examples Skin : Staph & Strep CAP : S. pneumoniae, H. flu, atypicals UTI: E. coli
Pathogen Risks Age Immune status Location Concomitant diseases Concomitant drugs
Case: Risks Chronic illness related Advanced age Diabetes Acute illness related Ventilator Surgery Drug related H2-blocker Morphine?
Case: Suspected pathogens Core pathogens Enterobacteriaceae H. flu, S. pneumoniae S. aureus* Pseudomonas Acinetobacter
Any other lab tests? Gram stains? Rapid Limited information Interpretation Preliminary culture results? Very helpful Often delayed Interpretation
General Approach 1. Infected? YES 2. Likely pathogens? Gram (-) enterics, Pseudomonas, S. pneumoniae, MSSA 3. Which initial antibiotic? 4. Now what?
Worsening Clinically deteriorating Increased ventilator support Fever increased, BP worsened Chest X-ray is worsening Culture results gram stain Gram (-) rods
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?
Drug Factors Spectrum General ever cover likely bugs Specific local, state, region sensitivities Site penetration CNS (Blood Brain Barrier) Lung?
Drug Factors Toxicity Ease of administration Oral Doses per day IV compatibility
Drug Factors Cost Drugs IV lines Monitoring (labs) Resistance costs
Combination Therapy Broaden coverage Synergy Preventing resistance Disadvantages
Multiple Drugs Combination Therapy Broaden coverage Ceftazidime plus metronidazole Gram (-) s + Anaerobes Cefepime plus vancomycin Gram (-) s + Gram (+) s
Bugs to Double Cover erratia seudomonas cinetobacter itrobacter nterobacter
Combination Therapy When does
Can you say
Synergy
Synergy
Synergy
Combination Therapy Negatives Toxicity of 2 drugs Antagonism
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
Case: Antibiotic choices Bugs to cover? Gram stain GNR Worst case is Pseudomonas Which drug(s) are best for Pseudomonas?
Case: What treatment to begin? Suggestions Aminoglycoside or fluoroquinolone plus Ceftazidime or cefepime Piperacillin Imipenem Aztreonam
Empiric decision Gentamicin 500 mg IV q24h Ceftazidime 2g IV q8h Await culture results
Case: monitoring After 24 hours of abx Stable, not cured Culture GNR Any changes??
Culture interpretation Growth Colonization, contamination, infection? No growth No infection? Antibiotics limit cultures Organisms difficult to grow Transient organisms
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
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
Case Continue therapy Stable patient Coverage of GNR reasonable Awaiting organism & antibiotic sensitivities
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
Improvement Fever WBC Clinical symptoms Radiologic may be slow
Route of administration Current IV drug available orally? Similar oral drug available? Criteria for oral therapy: Clinically stable/improving Afebrile 24-48 hours WBC GI tract O.K.
Case No oral forms Amikacin Imipenem No suitable oral alternatives Continual monitoring for side effects
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
Case: Duration of therapy Individualized to patient 14 days if responding quickly Can increase to 21 days if needed