Introduction to Antibiotic Therapy

Catherine Fleming, M.D.

Reasons to initiate antibiotics

Definite infection Probable diagnosis of infection Clinically ill patient (sepsis)
fever, hypotension, tachycardia neutropenia

Empiric vs definitive therapy

Empiric treatment:
antibiotics directed against an unknown pathogen and/or suspected infection

Definitive treatment:
antibiotics directed against a known pathogen

Principals of antibiotic Rx Step 1

What is the infection? Establish: 1. Infection vs non infectious illness 2. Suspected site

Use history/physical exam and investigatio

Principals of antibiotic Rx Step 2

What are the most likely microorganisms? - Probable bacterial pathogens for this infection - Likelihood of resistant bacteria: Community vs Hospital acquired (nosocomial) Host factors

Host Factors that Affect Treatment

- Risk for resistant or unusual flora
Immunosuppression Nosocomial infection Travel - Are any antibiotics contraindicated or require dose

adjustment

Allergies, Age, Renal function Liver disease, Pregnancy, lactation Drug interactions

Antibiotic Properties
Spectrum of activity Bactericidal or bacteriostatic Tissue Penetration Side effects Interactions Dosing regimen

Host factors: age

Neonate: decreased renal function Children: avoid drugs that affect bone/cartilage formation (tetracycline, quinolones) Elderly: decreased renal function, hearing impairment, poor absorption, increased AE

Host factors: renal function

Antibiotics may cause renal failure
tubular dysfunction-aminoglycosides acute interstitial nephritis- beta lactams

Dose adjustments may be required Suspect decreased creatinine clearance in diabetes, elderly

Allergies
10% population have Penicillin allergy rash can get cephalosporins Anaphylaxis/hives no cephalosporins

Host factors: liver disease

Hepatotoxicity: TB meds (INH), sulfa drugs (bactrim), tetracyclines Altered dosing for hepatically excreted drugs Suspect inapparent disease among alcoholics, hepatitis B & C infection

Pregnancy and lactation

Think pregnancy!! Safe drugs:beta lactams, macrolides, AG
Metronidazole > teratogen Chloramphenicol > grey baby syndrome Sulfa > kernicterus in 3rd trimester Tetracyclines > affects bone formation 3rd trimester through 8 years of age

Drug Interactions
Coumadin erythromycin, quinolone Theophylline macrolides, ciprofloxacin Phenytoin fluconazole rifampin OCP Ampicillin, rifampin Alcohol disulfiram-like metronidazole Seldane macrolides, ketoconazole

Drug factors: Spectrum of activity

Gram-positive versus Gram-negative Aerobic vs anaerobic Narrow spectrum versus extended spectrum Resistant to bacterial modifying enzymes:
- beta lactamase - aminoglycoside phosphotransferase (aph)

Penetration to site of infection

Bone: quinolones, clindamycin CNS: 3rd generation cephalosporins, newer macrolides, metronidazole, sulfa Kidney: all renally excreted drugs concentrate in the kidney

Additional antibiotic factors influencing choice

Side effect profile; Imipenim-seizures Septrin-bone marrow suppression Formulation;
Erythromycin IV-CHF Septrin

Dosing Schedule; Erythromycin qid vs Azithromycin qd Nafcillan Q4 hours vs Vancomycin bid Interactions

Choosing the correct antibiotic

Site of infection Likely pathogens Host factors Antibiotic properties Hospital Formulary Cost

Antibiotic Selection
Site of infection Probable pathogens Host factors:
age, renal and hepatic function allergies, pregnancy, medications

Antibiotic properties:
spectrum, penetration, interactions, side effects, dosing schedule, cost

Case 1A
A 24 year old woman presents with pain and burning with urination, urinary hesitancy, urgency and frequency. She is febrile to 102F, nauseated, vomiting, and dehydrated. On examination there is right costovertebral angle (CVA) tenderness.

Case 1A
She has a history of a urinary tract infection 3 years prior. There is no history of recent antibiotic use. She sexually active, not using birth control. She is allergic to penicillin

Case 1A
Likely diagnosis: pyelonephritis. She is admitted because of her inability to tolerate oral intake and dehydration. Urine and blood cultures are obtained. You are asked to prescribe appropriate antibiotics.

Case 1A
What is the infection: pyelonephritis What are the probable organisms: Gram (-): E coli, Klebsiella
Gram (+):Enterococci, Staph sapprophyticus Anaerobes:

antibiotic resistance unlikely

Case 1A
What host factors affect treatment ?
cannot take PO, and needs IV Rx sexually active ?? pregnant penicillin allergic, although need to determine what the allergy is

Case 1A
What drug factors affect treatment ? Appropriate spectrum activity: Appropriate renal penetration: hospital has 3 antibiotics against E. coli: gentamicin: an aminoglycoside ampicillin: a penicillin ciprofloxacin: a quinolone

Aminoglycosides (gentamicin)
Mode of action: bind to 30 S ribosome, bacteriocidal Spectrum of activity: aerobic Gram (-), synergy for Gram (+), no anaerobes Metabolism: excreted unchanged via kidney Distribution: poor tissue penetration Side effects: renal and ototoxic neuromuscular paralysis with succinylcholine Interactions:other nephro toxic drugs (furosemide)

Quinolones (ciprofloxacin)
Mode of action: DNA gyrase inhibition, bacteriocidal Spectrum of activity: Gram (-), moderate Gram (+). No anaerobes Distribution: good penetration eg bone, prostate Side effects: GI upset, photosensitivity, ? cartilage erosion in young Interactions: Coumadin, theophylline Restricted - resistance

Penicillins (ampicillin)
Mode of action: blocks cell wall synthesis Spectrum: streptococci, E coli, Enterococcus, oral anaerobes Distribution: extracellular, CNS Side effects:
Allergic: rash, anaphylaxis, interstitial nephritis CNS: seizures GI: diarrhea

Case 1A Antibiotic choice

Penicillin allergy: Nausea Pregnancy test: (-) No renal failure Vomiting ampicillin quinolone gentamicin IV

Of these: gent and amp preferable Quinolones restricted due to resistance

Case 1B
Your next patient is a 25 year old woman with a similar history except that she is currently taking amoxicillin for an ear infection (interchangeable with ampicillin) The hospital has >25% of E coli resistant to ampicillin

Case 1B
Choose either gentamicin or ciprofloxacin IV If she is discharged on oral ciprofloxacin, counsel her against suntanning (or choose another antibiotic)

Case 1A
The first woman was treated with ampicillin Two days into treatment urine cultures yield E coli resistant to ampicillin, but sensitive to gentamicin and ciprofloxacin What do you do ?

Case 2
An 85 year old man admitted 3 days ago after a fall is transferred to the medical service with fever and confusion. He is ill appearing with a fever of 103.6F and BP 120/80. Exam: enlarged prostate, indwelling foley Investigations: WBC 25k CXR clear.

Case 2
Likely infection: Pyelonephritis Likely pathogens:
E coli, Klebsiella, enterococci, hospital gram negatives Nosocomial infection increased chance of resistant organisms

Case 2
What host factors affect treatment?
Advanced age chance of baseline renal dysfunction (need to calculate Creatinine clearance) Medication interactions

Case 2
Choice of antibiotic: Gentamicin relatively contraindicated because of potential for renal dysfunction Ampicillin poor choice (for E coli or Klebsiella) because of risk of resistance ciprofloxacin

Case 3
56 year old alcoholic Admitted with fevers, cough and mental status changes x 24 hours Smoker, no IDU Examination: unkempt, thin Creps rt lung, bronchial breathing through out WCC 25k, cr 90, alt 40 ast 90, bili 25, alb 40, INR 1.0 HIV ()

Community acquired pneumonia

Likely organisms

Community acquired pneumonia

Likely organisms Pneumococcus H influenza Legionella Gram negatives Klebsiella E coli Staph aureus Anaerobes TB

Antibiotic choice
Normal renal function No allergies Liver function? No other meds Choice? Augmentin + klacid Cefotaxime + Klacid Cefotaxime + Moxifloxacin