Chapter 82

Basic Principles of Antimicrobial Therapy

Basic Principles of Antimicrobial Therapy

Define

Chemotherapy Antibiotic Antimicrobial agent Selective toxicity

Disruption of the bacterial cell wall Inhibition of an enzyme unique to bacteria Disruption of bacterial protein synthesis

Narrow spectrum antibiotic

Kills less bacteria A broad affect in microbes it destroys

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Broad spectrum antibiotic

Classification of Antibiotics
Drugs

work on

Cell wall synthesis Cell membrane permeability Protein synthesis Synthesis of nucleic acids Metabolism Viral enzymes

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Mechanisms of Microbial Drug Resistance

Microbes

may:

Develop drug metabolizing enzymes Stop uptake of drugs Change or decrease antibiotic binding and action at receptor sites Synthesizing compounds antagonistic to drug actions
Occurs

d/t changes in microbial genome

Spontaneous mutations or conjugation
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 Suprainfections

appears during the course of treatment for a primary infection. Normal flora destroyed allowing other infection to occur.

a new infection that

How

to delay the emergence of resistance:

Use antibiotics only when actually needed Narrow-spectrum whenever possible Reserve newer antibiotics

Selection of Antibiotics
Identify

organism - Cultures before any antibiotic is given Drug sensitivity of organism Match drug
with bug
Host

factors & Patient variables

Immune status Infection site Age Pregnancy & lactation; Genetic factors Allergy
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Selection of Antibiotics
Dosage

size

Penetration to site of infection M.I.C. minimal inhibitory concentration; usually 4-8 X MIC to be effective
Duration

of treatment

Multiple variables Imperative that antibiotics not be discontinued prematurely! Leads to drug resistance &/or reinfection

Misuses of Antimicrobial Drugs

Untreatable

infection Fever of unknown origin Improper dosage Lack identification of organism Omission of surgical drainage Patient non-compliance

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Chapter 83
Drugs That Weaken the Bacterial Cell Wall: Penicillins

Drugs That Weaken the Bacterial Cell Wall: Penicillins

Penicillins Weaken the cell wall by
Inhibition & Disinhibition (activation) Weaken cell wall allowing H2O to enter cell & ruptures No effect on mammalian cells

Bactericidal Prone

vs bacteriostatic

to bacterial resistance

Protein binding proteins Inactivation by enzymes (penicillinase or beta-lactamase)

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Classification of Penicillins
Penicillins Narrow-spectrum
Pencillinase sensitive(penicillin)
Broad Broad

spectrum spectrum

Pencillinase resistant(nafcillin)
Aminopenicillins(ampicillin)
Extended-spectrum

Antipseudomonal(ticarcillin)
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Penicillin G (Benzylpenicillin)
Know

three Forms

Potassium penicillin Procaine penicillin Benzathine penicillin

Therapeutic

uses

1st choice for gram + & some gram Pneumonia, meningitis, endocarditis, syphilis
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Pharmacokenetics

Absorption
Oral rare, unstable in acid, Penicillin V K IM or IV (need for high blood levels)

Distribution
Most tissues; needs inflammation to penetrate meninges, joints & eye

Elimination
Kidney; renal excretion prolonged w/ probenecid.

Side Effects
Least

toxic Pain @ injection site

nerves
Hyperkalemia

Avoid peripheral

or hypernatremia if given in large doses

caution in cardiac, renal & HTN pt.s

Drug

interactions reactions most common

aminoglycosides inactivation. Dont

infuse together in same IV solution
Allergic

Penicillin Allergy
NOT

dose dependent Types

Immediate (2-30 minutes) Accelerated (1-72 hours) Late (days or weeks)
Cross-sensitivity
Treatment

to cephlosporins

Epinephrine Respiratory support Preventionskin testing

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Penicillinase-Resistant Penicillins
Resistant

to inactivation by betalactamases Four Agents

Nafcillin, Oxacillin, Cloxacillin, Dicloxacillin
Very

narrow spectrum For staph infections MRSA - resistant to all PCNase drugs
Vancomycin w/ or w/o Rafampin
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Broad Spectrum Penicillins (Aminopenicillins)

The

aminopencillins consist of three agents

Ampicillin, Amoxicillin, Bacampicillin Strep, proteus mirablilis, E.coli, salmonella, shigella, & h. influenzae P.O. or parenteral

Adverse

effects

Rash Diarrhea
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Extended-Spectrum Penicillins
(Antipseudomonal Penicillins)
The

extended-spectrum penicillins consist of four agents:

Ticarcillin, Carbenicillin indanyl, Mezlocillin, Piperacillin Mostly for Pseudomanas infection
Aminoglycoside added to regime Do not mix together

Adverse effects

allergic reactions, sodium overload, interferes with platelet function

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Chapter 84
Drugs That Weaken the Bacterial Cell Wall: Cephalosporins and Vancomycin

Drugs that Weaken the Bacterial Wall:

Cephalosporins and Vancomycin
Cephalosporins

Similar to penicillin structure

Beta-lactam antibiotics Bactericidal Broad spectrum w/ low toxicity
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Classification of Cephalosporins
First

generation

Gram+, staph & strep

Cefazolin (Ancef)
Second generation some pneumonia, otitis, sinusitis, RTIs, PID, abd. infections

Cefaclor (Ceclor)
Third generation Drugs of choice for meningitis & nosocomal; avoid routine use

Cefoperazone (Cefobid)
Fourth

generation

Cefepime (Maxipime)
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Pharmacokenetics
Absorption

Poor PO absorption; most given IM or IV

Distribution - well to most tissues; 3rd & 4th generation good CSF Elimination

except cefoperzaone & ceftriaxone (Rocephin)

-- kidney

Adverse effects
Allergy

PCN

rash; cross-sensitivity to

Bleeding Thrombophlebitis

w/ IV infusion

Rotate sites, administer slowly diluted

Drug interactions
Probenecid; Alcohol; anticoagulants

Cephlosporins
Therapeutic Uses Broad-spectrum
Bactericidal OK w/ mild PCN allergies Third generation preferred
Drug

Selection

24 in use! No major difference, just costs

Vancomycin (Lyphocin)
Action

Cell wall synthesis

Uses

Severe infections Pseudomembranous colitis (C. difficile, MRSA)

Adverse

effects

Ototoxicity Thrombophlebitis Allergy

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Chapter 85
Bacteriostatic Inhibitors of Protein Synthesis: Tetracyclines, Macrolides, and Others

Bacteriostatic Inhibitors of Protein Synthesis:

Tetracyclines, Macrolides, Clindamycin and Chloramphenicol
Uses Tetracyclines Rickettsial disease Broad spectrum Chlamydia Trachomatis antibiotic Brucellosis Inhibits protein Cholera synthesis Mycoplasma
suppresses growth bacteriostatic

pneumonia Lyme disease Helicobacter pylori acne

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Pharmacokinetics
Absorption

stomach

good p.o. on EMPTY

Chelation -- Calcium, iron, magnesium, aluminum, zinc

Distribution

all tissues, poor CSF; crosses placenta

renal for short & intermediate; hepatic for long-acting

Elimination

 Duration

Tetracyclines

Short-acting Long-acting
Adverse

effects

Gastrointestinal Hepatotoxicity Renal toxicity Bones & teeth stains developing teeth

(< 8 years & pregnancy); reversible long-bone growth in premies Photosensitivity

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Tetracyclines Adverse Effects

Major

Precautions in:

USUALLY CONTRAINDICATED

Pregnancy & PostPartum women; Kidney disease / Renal patients Can cause liver disease Children under 8 years of age Suprainfection of bowel

Macrolides (Erythromycin)
Broad Use

bacteriostatic

spectrum antibiotic

if allergic to penicillin Gram + some gram Administration P.O. & IV; GI upset Distribution most tissues & fluids; poor
CSF; crosses placenta, but no adverse effects
Elimination

hepatic, some renal

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Erythromycin
Adverse

effects

Gastrointestinal take w/ food Superinfection Drug interactions

Increases

life of some drugs (Inhibitor) Avoid w/ non-sedating antihistamines Theophylline, carbamazipine, warfarin w/ care Do not give w/ chloramphenical or clindamycin

Clindamycin (Cleocin)
Inhibits

protein synthesis

bacteriostatic

Anaerobic

bacteria PO, IM, IV & vaginal preps

Can

induce antibiotic-associated pseudomembranous colitis Adverse effects

Hepatic toxicity Renal toxicity
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Chapter 86
Aminoglycosides: Bactericidal Inhibitors of Protein Synthesis

 Narrow

spectrum antibiotic Bactericidal Use: aerobic gram-negative bacilli,

anaerobes
Absorption

Aminoglycosides: Bactericidal Inhibitors of Protein Synthesis

no

IM or IV, poor PO only has most extracellular fluids; kidneys

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local effect

not usually given

Distribution

nephrotoxic

Elimination

Peak & Trough

Measure

effects Peak drawn after administration

IM 1 hour IV -- 30 mins Not to exceed 12 mcg/ml
Trough

levels of drug to avoid toxic

administration

drawn prior to next

Hold if exceeds 2 mcg/ml

Aminoglycosides
Adverse

effects

Ototoxicity Important indicator of toxicity Nephrotoxicity Hypersensitivity reactions

Drug

interactions:

PCN, oto/nephro/ toxic drugs,; skeletal muscle relaxants (intensify

causing respiratory arrest)

Gentamicin (Garamycin)
Serious

infections caused by aerobic gram-negative bacilli Uses

Pseudomonas aeruginosa

Escherichia Coli
Klebsiella Serratia
Adverse

effects
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Nephrotoxicity

Ototoxicity

Chapter 87
Sulfonamides and Trimethoprim

Sulfonamides and Trimethoprim (Gantrisin)

Broad

spectrum antibiotics Suppress bacterial growth - inhibiting of folic acid Urinary tract infections e.coli Absorption PO & topical Distribution all tissues & placenta Excretion -- kidney
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Sulfonamides and Trimethoprim

Adverse

effects

Hypersensitivity reactions StevensJohnson syndrome Blood dyscrasias hemolytic anemia Kernicterus Crystalluria
Drug

interactions

intensifies warfarin, phenytoin, & oral hypoglycemics

Trimethoprim-Sulfamethoxazole
(TMP-SMZ) (Bactrim)
Trimethoprim

sulfamethoxazole (Bactrim, Septra)

synthesis of tetrahydrofolic

Inhibits

acid

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Trimethoprim-Sulfamethoxazole
(TMP-SMZ) (Bactrim)
Uses

Urinary tract infection

Montezumas revenge

Pneumocystis carinii
Adverse

(HIV prophylaxis)

effects

Gastrointestinal Rash

Chapter 88
Drug Therapy of Urinary Tract Infections

Drug Therapy of Urinary Tract Infections

Urinary

tract infections Complicated or uncomplicated Upper

Acute pyelonephritis Acute bacterial prostatitis
Lower

Acute cystitis Acute urethral syndrome

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Urinary Tract Antiseptics

Nitrofurantoin (Furadantin, Macrodantin, macrobid)

Methenamine

(Mandelamine) Nalidixic acid (NegGram) Cinoxacin (Cinobac)

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Nitrofurantoin (Furadantin)
(A.K.A. Macrodantin)
Bacteriostaticlow

concentrations Bactericidalhigh concentrations Useslower tract UTIs Adverse effects generally safe
Gastrointestinal effects Pulmonary reactions Hematologic effects Peripheral neuropathy
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Methenamine (Mandelamine)
Decomposes

into ammonia and formaldehyde denaturing of bacteria Uses: chronic lower UTIs Adverse effects
Safe Well tolerated Contraindicatedrenal patient

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Chapter 89
Antimycobacterial Agents:

Drugs for Tuberculosis

Antimycobacterial Agents:
Drugs for Tuberculosis, Leprosy, and Mycobacterium avium Complex Infections
Tuberculosis

Mycobacterium tuberculosis Person to person Inhaled infected aerosol

Screening

Tuberculin skin test (PPD)

Diagnosis

Cytology Chest x-ray

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Drug Resistance with Tuberculosis

Goal

of treatment

Eliminate symptoms Prevent relapse

Drug

resistance

Contact-person with resistant TB Repeated ineffectual courses of treatment

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Causes of Drug Resistance

Principal cause underlying the emergence of resistance is inadequate drug therapy.

Must always use at least two drugs in therapy

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Treatment Regimens for Tuberculosis

Two

Phases
active tubercle bacilli intracellular persisters

Induction phases
Eliminate

Continuation phase
Eliminate

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Drug-Sensitive Regimen for Tuberculosis

Induction

2 months Daily therapy

phase

Continuation

phase 4 months
or biweekly
Isoniazid Rifampin

Isoniazid Rifampin Pyrazinamide Ethambutol

Daily

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Multidrug-Resistant Regimen for Tuberculosis

Define

Initial therapy
Isoniazid Rifampin Pyrazinamide Ethambutol Kanamycin Cycloserine

Resistance Isoniazid and Rifampin

Treatment

3 drugs for 1-2 yrs

Para-aminosalicylic

acid Ciprofloxacin
B

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Isoniazid (Laniazid) (INH)

Primary

mycobacterium

agent

highly selective to

Bactericidal to actively dividing organisms Therapeutic

Only for treatment and prophylaxis of TB; take in combination with at least one other drug
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use

Adverse effects of INH

Peripheral neuropathy
Dose-related is most common; paresthesias; prophylaxis with pyridoxine (B6)

Hepatotoxicity Other adverse effects

CNS effects, anemia, GI distress, dry mouth, and urinary retention and allergy

Drug interactions
Phenytoin; Alcohol, rifampin, and pyrazinamide Increases risk of hepatotoxicity

Rifampin (Rifadin)
Broad Uses

spectrum antibiotic

bactericidal

Tuberculosis Leprosy Haemophilus influenzae Legionella

Adverse

effects

Hepatitis Discoloration of body fluids * Drug interactions INH & pyrazinamide; INDUCER B Menu

Ethambutol (Myambutol)
Bacteriostatic

Uses:

tuberculosis Adverse effects

Optic neuritis Allergy Hyperuricemia

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Chapter 90
Miscellaneous Antibacterial Drugs: Fluoroquinolones and Metronidazole

Miscellaneous Antibacterial Drugs: Fluoroquinolones & Metronidazole Fluoroquinolones Ciprofloxacin (Cipro)

Narrow spectrum antibiotic Bactericidal (Inhibits bacterial DNA replication)
Uses:

multi-system infections Adverse effects

Gastrointestinal Headache Candidia can occur Seizures have occurred Contraindicated in pregnancy & < 18y.o
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Fluoroquinolones
Drug

and Food interactions

Absorption reduced by:

Aluminum antacids

Magnesium antacids
Iron or Zinc salt Sucralfate

Milk and dairy products

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Metronidazole (Flagyl)
Bactericidal

& protozoalcidal

Uses

Protozoal infections Infections caused by obligate anaerobes Helicobacter pylori

Adverse

effects

Neurotoxicity Allergy Superinfections Avoid Alcohol

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Chapter 91
Antifungal Agents

Antifungal Agents
Two

major groups

Systemic mycotic infections

Opportunistic Non-opportunistic

Superficial mycotic infections

Candidiasis Dermatophytes

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Amphotericin B (Fungizone)
Broad

spectrum fungal agent Highly toxic -- only given IV Uses: systemic mycoses Adverse effects
Infusion reactions Nephrotoxicity Hypokalemia
Drug

nephrotoxic drugs

interactions avoid other

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Ketoconazole (Nizoral)
Oral

alternative for systemic mycoses w/ less side effects Very slow response Absorption need acidic environment Adverse effects - well tolerated (*Inhibitor)
Hepatotoxicity Endocrine effects
gynecomastia

in men; menstrual irregularities

Fluconazole (Diflucan)
Azole

group of antifungal agents Fungistatic Adverse effects

Nausea Headache Vomiting Abdominal pain

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Drugs for Superficial Mycoses

Dermatophytic

infections

(ringworm)

Tinea Tinea Tinea Tinea

pedis corporis cruris capitis

Candidia

infections; thrush

species

vulvovaginal

Onychomycosis

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Tinea pedis

Tinea corporis

Tinea cruris
(aka Jock Itch)

Tinea capitis

Drugs for Superficial Infections

Azoles
ketoconazole P.O. , miconazole.

(topical) Clotrimazole,

Skin, mouth & vaginal tx Adverse effects low risk for but stinging, erythema, edema, urticaria, pruritus & peeling

Griseofulvin
Griseofulvin (Fulvicen)oral Superficial mycoses dermatophytic infection Ineffective systemic mycoses Inhibits fungal mitosis
3-8 wks for skin; up to 1 year for nails

Adverse effects
Transient headache Rash Gastrointestinal
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Chapter 94
Drug Therapy of Sexually Transmitted Diseases

Drug Therapy of Sexually Transmitted Diseases

Sexually

transmitted diseases (STDs)

Infections transmitted through sexual contact

Types

of STDs

Chlamydia trachomatis Gonococcal infections Pelvic inflammatory disease Trichamoniasis Syphilis

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Figure 91-1: Incidence of Sexually Transmitted Diseases

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Chlamydia trachomatis
Most

common bacterial STD in U.S.

Causes

Genital tract infections Proctitis Conjunctivitis

Treatment

Azithromycin (Zithromax) Doxycycline (Vibramycin)

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Gonococcal Infections
Neisseria Causes

gonorrhoeae

Urethral, cervical, and rectal infection Pharyngeal infection Conjunctivitis

Treatment

Cefixime (Suprax)

Its Back!!!

Ceftriaxone (Rocephin)
Ciprofloxacin (Cipro) Ofloxacin (Floxin)
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Pelvic Inflammatory Disease

Syndrome

including endometritis, pelvic peritonitis, tubo-ovarian abscess and inflammation of the fallopian tubes Neisseria gonorrhoeae Chlamydia trachomatis

Cause

Treatment

in-patient
2nd generation

Cefotetan (Cefotan)
2 Gm q12 IV

Doxycycline

PO or IV
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Trichomoniasis Vaginalis

Cause
T. vaginalis

S&S: Frothy, yellow

or green discharge, odor, itching, dysuria in women; men asymptomatic Treatment
Metronidazole (Flagyl) 2 gm single dose PO

Syphilis

Cause
Treponema pallidum spirochete

Treatment
Penicillin G IM (Benzethine PCN)

Chapter 95

Antiseptics and Disinfectants

Antiseptics and Disinfectants

Define

Antiseptic Disinfectant Sterilization Germicide Germistatic

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Ideal Antiseptic
Safe

Effective
Selective Germicidal Broad

spectrum of antimicrobial activity

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Common Antiseptics and Disinfectants

Alcoholethanol

Aldehydesglutaraldehyde
Iodine

(Cidex)

compounds Chlorine compounds Phenols Hydrogen peroxide

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