Transcript Bugs and Drugs A Review of Antibiotics

BUGS AND DRUGS
A REVIEW OF ANTIBIOTICS
Curtis M. Grenoble, MHS, PA-C
Lock Haven University
LECTURE OUTLINE
 Mechanisms
of Action
 Mechanisms of Resistance
 Bacterial Resistance
 Principles of Therapy
 Choosing an Antibiotic
 Gram positives, gram negatives & anaerobes
 Case Scenarios
MECHANISMS OF ACTION
 Goal
of antibiotic treatment:
Limit host toxicity
 Maximize specific microbe toxicity

 Bacteriocidals
kill bacteria
 Bacteriostatics

inhibit further growth
Allowing immune system to regain control
MECHANISMS OF ACTION
 Common

bacteriocidals
β-Lactams
Penicillins
 Cephalosporins
 Carbapenems
 Monobactams


Aminoglycosides
MECHANISMS OF ACTION
 Common




bacteriostatics
Sulphonamides
Tetracyclines
Chloramphenicol
Macrolides
Erythromycin
 Clarithromycin
 Azithromycin


Trimethoprim (often used along with
sulfonamides i.e. Bactrim)
MECHANISMS OF RESISTANCE
 Intrinsic
Resistance
Analogous to innate (non-specific) human immunity
 Examples:

Obligate anaerobic bacteria to aminoglycosides
 Gram (–) bacteria to vancomycin

 Acquired
Resistance
Analogous to specific action of human immunity
 Bug, over time, develops resistance to specific mechanism of
action

Mutation of resident genes, or
 Acquire new genes and incorporate into own DNA


Major problem with over-prescribing antibiotics
Pt demands (stronger) antibiotic and practitioner gives in (viral URI,
viral pharyngitis)
 Selects for those organisms with resistance, proliferation, further
mutation

PRINCIPLES OF ANTIBACTERIAL THERAPY

First, attempt to specifically ID the bug if accessible


Obtain culture
Stain specimen and ID under microscope
Cocci
 Bacilli

C&S
 Choose narrowest spectrum
and most inexpensive drug
that will effectively eliminate
the infection.

PRINCIPLES OF ANTIBIOTIC THERAPY

Susceptibility


If peak serum concentration of drug is 4-times the MIC
(Minimum Inhibitory Concentration)
Breakpoint

Concentration of antibiotic that separates susceptible from
resistant bacteria
PRINCIPLES OF ANTIBACTERIAL THERAPY
 Pharmacodynamics

Concentration dependent


e.g. Aminoglycoside once daily
Time dependent
e.g. Amoxil for pneumococcal AOM
 Need to maintain high levels of abx over MIC x number of days
 More difficult for drug to reach inner ear
 Younger male with UTI
 TB therapy

PRINCIPLES OF ANTIBIOTIC THERAPY

Site of Infection – Difficult to treat

Meningitis – blood-brain barrier, some don’t cross at all,
others not enough

Bacterial endocarditis – Growth may be difficult to penetrate
and often possess both innate and acquired immunity

Osteomylitis – dense tissue, low vascularity

Intraocular infections – no blood in vitreous, special vessels
mediate exchange of nutrients with vitreous

Abscesses – encapsulated, thick, fibrous, poorly vascularized

Need to I&D
PRINCIPLES OF ANTIBACTERIAL THERAPY

Site of Infection – Easy to Treat

Urinary Tract Infection
High drug concentration in urine due to elimination via kidneys
 In the past, PCN purified from urine to reuse before made
synthetically

PRINCIPLES OF ANTIBACTERIAL THERAPY

Empiric Therapy

Life-threatening infection


Need to treat immediately with best guess of causative organism
 Based on signs, symptoms and epidemiology
 Need to know most likely causative organism in a given institution
Community-acquired Infection

Need to know most likely causative organism in:
 Community
 Population
 Age group
CHOICE OF ANTIBACTERIAL DRUGS
 β-Lactams

Penicillins
β-lactamase susceptible – Penicillin G (parenteral) V (oral), ampicillin,
amoxicillin, ticarcillin
 β-lactamase resistant – Methicillin, oxacillin, nafcillin, cloxacillin,
dicloxacillin
 Amoxicillin-Clavulanic acid (Augmentin)


Cephalosporins
1st Generation – Cephalexin, cephradine, cephadroxil
 2nd Generation – Cefaclor, cefoxitin, cefuroxime, cefdinir, ceftibuten
 3rd Generation – Ceftriaxone
th
 4 Generation - Cefepime


Carbapenems


Imipenem, meropenem, ertapenem
Monobactams

Aztreonam
CHOICE OF ANTIBACTERIAL DRUGS

Non-β-Lactams

Vancomycin

Aminoglycosides – streptomycin, gentamicin, tobramycin

Macrolides and Ketolides – erythromycin, azithro-, telithro-

Licosamides – clindamycin

Chloramphenicol

Tetracyclines – tetracyclin, doxycycline, minocycline

Fluoroquinolones – ciprofloxacin, gati-, moxi-, levo-, etc

Rifampin

Metronidazole
CHOICE OF ANTIBACTERIAL DRUGS

Penicillin G and V Spectrum

Spirochetes
Treponema pallidum (Syphilis)
 Borrelia (Lyme Dz)


Streptococci
Groups A and B
 Many strains of S. pneumoniae



Clostridium species
Penicillin G and V Sensitive Diseases



Syphilis
Strept infections groups A and B
Tetanus
CHOICE OF ANTIBACTERIAL DRUGS
 Ampicillin
Spectrum
Enterococcus faecalis
 Salmonella
 Haemophilus influenzae

 Ampicillin




Diseases
E. faecalis UTI
Salmonellosis
H. flu AOM & epiglottitis
Amoxicillin-Clavulanic Acid (Augmentin)
Pasturella multocida
 Dog/Cat bite
 Wounds obtained in wet environment

CHOICE OF ANTIBACTERIAL DRUGS

1st Generation Cephalosporins Spectrum
Escherichia Coli
 Klebsiella pneumoniae
 Proteus mirabilis


1st Generation Cephalosporins Diseases





Community acquired UTI
UTI secondary to indwelling bladder catheter
Klebsiella pneumoniae pneumonia (alcoholics, DM, lung dz)
Abdominal infection
Surgical site/soft tissue infection
CHOICE OF ANTIBACTERIAL DRUGS

Oral 2nd Generation Cephalosporins Spectrum



Gram positive cocci (streptococci, staphylococci)
Haemophilus influenzae
Oral 2nd Generation Cephalosporins Diseases
Otitis media
 Sinusitis
 Lower respiratory tract infection

CHOICE OF ANTIBACTERIAL DRUGS

Parenteral 3rd Generation Cephalosporins Spectrum




Enteric gram-negative rods
Pseudomonas
Listeria
Parenteral 3rd Generation Cephalosporins Diseases
Gonorrhea (Ceftriaxone)
 Salmonellosis
 Listeria bacterial menningitis

CHOICE OF ANTIBACTERIAL DRUGS

4th Generation Cephalosporins Spectrum





Gram-positive bacteria
Gram-negative bacteria
P. aeruginosa
Enterobacteriaceae
4th Generation Cephalosporins Diseases
Intra-abdominal infections
 Respiratory tract infections
 Skin infections

CHOICE OF ANTIBACTERIAL DRUGS
 Vancomycin

Spectrum
Gram-positive cocci (enterococci, streptococci, staphylococci)
 Vancomycin
Diseases
Methicillin-resistant staph aureus
 Second-line for most gram-positive
 P.O. in pseudomembranous colitis

Not absorbed when taken P.O.
 Becomes “topical” tx for UC

Use Vanco sparingly and only in demonstrated cases of
resistance to β-lactams to prevent MRSA from developing
resistance
 Not for routine empiric therapy

CHOICE OF ANTIBACTERIAL DRUGS

Aminoglycoside spectrum
Gram-negative aerobes
 Staph
 No activity against anaerobic bacteria or in acidic/low oxygen


Aminoglycoside diseases
SevereURI
 Gram-neg bacteremia
 Tularemia, plague, brucellosis – Streptomycin (2nd line TB)

CHOICE OF ANTIBACTERIAL DRUGS

Macrolides spectrum (bacteriostatic)
Gram-positive bacteria
 Legionella
 Chlamydia
 Helicobacter pylori


Macrolides diseases
Strept pharyngitis in PCN-allergic (erythromycin- don’t
need broader spectrum if not indicated)
 Community-acquired pneumococcal pneumonia
 Legionnaire’s disease
 Gastric ulcers

CHOICE OF ANTIBACTERIAL DRUGS

Tetracyclines spectrum (bacteriostatic)
Gram-positive bacteria
 Gram-negative bacteria
 Borrelia (Lyme disease)
 Chlamydia


Tetracyclines diseases





Bacterial chronic bronchitis
Lyme disease
Skin and soft-tissue infections
Syphillis
Acne vulgaris – suppresses resident P. acnes flora, prevents
from chopping non-irritating long chain FA to irritating
short-chain FA
CHOICE OF ANTIBACTERIAL DRUGS

Sulfonamides & Trimethoprim spectrum




E. Coli
H. flu
Other gram-neg bacteria
Sulfonamides & Trimethoprim diseases
Community-acquired UTI (Bactrim)
 Otitis media
 Bacterial URI

CHOICE OF ANTIBACTERIAL DRUGS

Fluoroquinolones spectrum
Pseudomonas aeruginosa
 Other gram-neg bacteria


Fluoroquinolones diseases
UTI
 Bacterial gastroenteritis
 Community-acquired pneumonia

CHOICE OF ANTIBACTERIAL DRUGS

Metronidazole spectrum





Anaerobic bacteria only
Mostly gram-negative
Bacteroides species
Also an anti-parasitic
Metronidazole diseases
Tough to treat anaerobic abscesses of abdomen, brain or lung
 Bacterial vaginosis
 Drug of choice: Antibiotic-associated pseudomembranous
colitis

DURATION OF THERAPY & TREATMENT
FAILURE VS. SUCCESS

Treatment duration varies according to disease



Duration



Refer to drug guides for dosage and duration
No trials for many diseases, therefore duration not firmly
established
Not too short – need to fully treat/resolve infection
Need to avoid resistance
Success = no relapse when treatment is d/c

New infection with different organism is considered a
success for initial infection
Failure = recurrence of infection with identical
organism
 Failures need >4 wk course & combination treatment

COMMON SIDE-EFFECTS AND ADVERSE
REACTIONS

All antibiotics can elicit allergic responses
Mild, annoying rashes, etc.
 Anaphylaxis
 Stevens-Johnson syndrome


All antibiotics target normal flora in addition to
pathogens
May lead to overgrowth of Candida – Yeast Infxn
 May lead to overgrowth of Clostridium difficile

Mild diarrhea to severe life-threatening complications
(pseudomembranous colitis)
 D/C offending antibiotic
 Supportive therapy
 Drug of choice: Metronidazole (Vancomycin 2nd line)

COMMON SIDE-EFFECTS AND ADVERSE
REACTIONS

β-Lactams




1-4% of treatment courses result in allergic reaction
Severe: anaphylaxis, TEN, Stevens-Jonhnson syndrome,
pseudomembranous colitis (rare)
Mild: rash, GI upset, diarrhea
Vancomycin
Red Man Syndrome – pruritus, flushing, erythema
 Phlebitis at infusion site
 Nephrotoxicity and Ototoxicity rare


Aminoglycosides
Nephrotixicity – accumulation in peritubular space
 Ototoxicity – can destroy hair cells, auditory/vestibular
 Neuromuscular depression with rare respiratory depression

COMMON SIDE-EFFECTS AND ADVERSE
REACTIONS

Macrolides





Serious adverse reactions very rare
GI side effects – burning, nausea, nomiting (up to 50% of pts)
Hepatotoxicity and ototoxicity rare
QT Prolongation
Lincosamides
GI distress
 Pseudomembranous colitis secondary to C. diff toxin
(Metronidazole)


Chloramphenicol
Bone marrow suppression
 Gray syndrome (cyanosis, hypotension, death) – infants

COMMON SIDE-EFFECTS AND ADVERSE
REACTIONS

Tetracyclines

Contraindicated in children <8 yrs old

Mottling of permanent teeth
Contraindicated in pregnancy – teratogenicity
 GI distress
 Phototoxic skin reactions


Sulfonamides and Trimethoprim
Generally safe
 Minor skin rashes to erythema multiforme and SJS, TEN
 Hematologic complications – agranulocytosis, anemia
 Renal insufficiency caused by crystal formation

COMMON SIDE-EFFECTS AND ADVERSE
REACTIONS

Fluoroquinolones
Warning:
Cautious use of Fluoroquinolones due to risk of tendon ruptures
associated with their use. Contraindicated for use in pregnant women
and patients < 18 yrs of age because of evidence of cartilage damage in
developing joints.




GI distress – nausea, diarrhea (<5%)
CNS effects – insomnia, dizziness (<5%)
Phototoxicity
Metronidazole
GI distress – nausea
 Metallic taste, stomatitis, glossitis
 Contraindicated in pregnancy - mutagenicity

CASE SCENARIO 1

30 year-old male presents with dysuria and a painful,
swollen testicle that is red and tender.

Diagnosis?

Bug?

Drug?
CASE SCENARIO 1

30 year-old male presents with dysuria and a painful,
swollen testicle that is red and tender.

Diagnosis? Orchitis

Bug? Neisseria gonorrhoeae or Chlamydia trachomatis

Drug? Ceftriaxone & Doxycycline
CASE SCENARIO 2

A 50 year-old lifetime smoker presents with productive
cough of dark, jelly-like sputum. He has rales in the
right upper lung field. His CXR reveals a RUL
infiltrate.

Diagnosis?

Bug?

Drug?
CASE SCENARIO 2

A 50 year-old lifetime smoker presents with productive
cough of dark, jelly-like sputum. He has rales in the
right upper lung field. His CXR reveals a RUL
infiltrate.

Diagnosis? Pneumonia

Bug? H. influenza

Drug? Levofloxacin (Levaquin) or Ceftriaxone or
Augmentin
CASE SCENARIO 3

A 12 year-old girl suffers a cat bite to her LIF (left index
finger). The fingers are flexed and there is redness and
tenderness along the flexor tendon surface extending
into the forearm. She cannot extend the finger.

Diagnosis? Tenosynovitis

Bug? Pasturella

Drug? Amoxicillin/Clavulanic Acid (Augmentin)
CASE SCENARIO 4

A 35 year-old, healthy, recently sexually active female
develops dysuria, urgency, and polyuria. She has
suprapubic tenderness and is afebrile.

Diagnosis?

Bug?

Drug?
CASE SCENARIO 4

A 35 year-old, healthy, recently sexually active female
develops dysuria, urgency, and polyuria. She has
suprapubic tenderness and is afebrile.

Diagnosis? UTI

Bug? E. Coli

Drug? Bactrim
CASE SCENARIO 5

A 17 year-old returns from a rock concert where
hundreds of people camped outside near a stream
overnight. She has abdominal pain, high fever, and
severe, bloody diarrhea.

Diagnosis?

Bug?

Drug?
CASE SCENARIO 5

A 17 year-old returns from a rock concert where
hundreds of people camped outside near a stream
overnight. She has abdominal pain, high fever, and
severe, bloody diarrhea.

Diagnosis? Gastroenteritis

Bug? Shigella

Drug? Ciprofloxacin
CASE SCENARIO 6

A middle-aged man returns for a third episode of a
painful, red, warm nodule on the nape of his neck tha
recurs despite antibiotics and I&D.

Diagnosis?

Bug?

Drug?
CASE SCENARIO 6

A middle-aged man returns for a third episode of a
painful, red, warm nodule on the nape of his neck tha
recurs despite antibiotics and I&D.

Diagnosis? Furuncle/Carbuncle

Bug? MRSA

Drug? Vancomycin
CASE SCENARIO 7

A 32 year-old nonsmoker complains of a cough of 3
weeks duration. Placed on amoxicillin 10 days ago
without relief. Pt is afebrile.

Diagnosis?

Bug?

Drug?
CASE SCENARIO 7

A 32 year-old nonsmoker complains of a cough of 3
weeks duration. Placed on amoxicillin 10 days ago
without relief. Pt is afebrile.

Diagnosis? Pertussis (whooping cough)

Bug? Bordatella pertussis

Drug? Erythromycin
CASE SCENARIO 8

An elderly male from an ECF is hospitalized. He
suffered a CVA and has altered consciousness. 2 days
s/p admission, he becomes febrile and septic. CXR
shows large upper lobe infiltrates.

Diagnosis?

Bug?

Drug?
CASE SCENARIO 8

An elderly male from an ECF is hospitalized. He
suffered a CVA and has altered consciousness. 2 days
s/p admission, he becomes febrile and septic. CXR
shows large upper lobe infiltrates.

Diagnosis? Aspiration pneumonia

Bug? Bacteroides fragilis

Drug? Clindamycin
CASE SCENARIO 9

A healthy young adult male marathon runner steps on a
nail that punctures his running shoe producing a wound
in the sole of his left foot. The wound becomes reddened,
warm and painful. The infection is localized around the
puncture site on exam and the patient’s exam is
otherwise normal.

Diagnosis?

Bug?

Drug?
CASE SCENARIO 9

A healthy young adult male marathon runner steps on
a nail that punctures his running shoe producing a
wound in the sole of his left foot. The wound becomes
reddened, warm and painful. The infection is localized
around the puncture site on exam and the patient’s
exam is otherwise normal.

Diagnosis? Puncture wound, wet environment

Bug? Pseudomonas aeruginosa

Drug? Augmentin (or Cefepime)
CASE SCENARIO 10

A young healthy female was seen by you in the office one
week ago for an uncomplicated acute cystitis. You
prescribed a 3-day course of Macrodantin, which she
finished. A day after finishing the medication, she
developed severe diarrhea and sees you that day again
in the office. She denies recent travel, dietary changes,
or exposure to sick persons. She has a fever, looks sick,
and has general abdominal tenderness. You admit her
to the hospital for treatment.
Diagnosis?
 Bug?
 Drug?

CASE SCENARIO 10

A young healthy female was seen by you in the office one
week ago for an uncomplicated acute cystitis. You
prescribed a 3-day course of Macrodantin, which she
finished. A day after finishing the medication, she
developed severe diarrhea and sees you that day again in
the office. She denies recent travel, dietary changes, or
exposure to sick persons. She has a fever, looks sick, and
has general abdominal tenderness. You admit her to the
hospital for treatment.
Diagnosis? Pseudomembranous colitis (abx enterocolitis)
 Bug? Clostridium difficile
 Drug? Metronidazole

CASE SCENARIO 11
A 29 year-old sexually active heterosexual female returns
from hiking in the Mid-Atlantic region in the spring. One
day after hiking, she notes an attached, engorged tick on
her body, and removes the tick. Seven days later she
develops a bull’s eye rash on her trunk, myalgias, fatigue,
and sees you in the office that day. She is otherwise
healthy and her last menstrual period was two months
ago. You are seeing her in a mobile medical van and do
not have the availability of any immediate diagnostic
tests. She has no signs of serious systemic infection but
does have the described rash with no other skin
abnormalities and a mild fever.
 Diagnosis?
 Bug?
 Drug?

CASE SCENARIO 11
A 29 year-old sexually active heterosexual female
returns from hiking in the Mid-Atlantic region in the
spring. One day after hiking, she notes an attached,
engorged tick on her body, and removes the tick. Seven
days later she develops a bull’s eye rash on her trunk,
myalgias, fatigue, and sees you in the office that day.
She is otherwise healthy and her last menstrual period
was two months ago. You are seeing her in a mobile
medical van and do not have the availability of any
immediate diagnostic tests. She has no signs of serious
systemic infection but does have the described rash with
no other skin abnormalities and a mild fever.
 Diagnosis? Lyme disease
 Bug? Borrelia burgdorferi
 Drug? Amoxicillin (not doxy – may be pregnant)
