This document lists common bacteria that cause infections in different body sites. In the mouth, common bacteria include Peptococcus, Peptostreptococcus, and Actinomyces. On the skin and soft tissues, common bacteria are S. aureus, S. pyogenes, and S. epidermidis. In bones and joints, common bacteria are S. aureus, S. epidermidis, streptococci, N. gonorrhoeae, and gram-negative rods. In the abdomen, common bacteria are E. coli, Proteus, Klebsiella, Enterococcus, and Bacteroides species. In the urinary tract, common bacteria are E. coli, Proteus

1. Common Bacteria by Site of Infection
Mouth
Peptococcus
Peptostreptococcus
Actinomyces
Skin/Soft Tissue
S. aureus
S. pyogenes
S. epidermidis
Pasteurella
Bone and Joint
S. aureus
S. epidermidis
Streptococci
N. gonorrhoeae
Gram-negative rods
Abdomen
E. coli, Proteus
Klebsiella
Enterococcus
Bacteroides sp.
Urinary Tract
E. coli, Proteus
Klebsiella
Enterococcus
Staph saprophyticus
Upper Respiratory
S. pneumoniae
H. influenzae
M. catarrhalis
S. pyogenes
Lower Respiratory
Community
S. pneumoniae
H. influenzae
K. pneumoniae
Legionella pneumophila
Mycoplasma, Chlamydia
Lower Respiratory
Hospital
K. pneumoniae
P. aeruginosa
Enterobacter sp.
Serratia sp.
S. aureus
Meningitis
S. pneumoniae
N. meningitidis
H. influenza
Group B Strep
E. coli
Listeria

2. Protein Synthesis Inhibitors
Tetracyclines Macrolides
Chloramphenicol Aminoglycosides
Clindamycin Streptogramins

3. Tetracyclines - Structure
Excretion
R1 R2 R3 R4 mg/hr
tetracycline (Achromycin) H OH CH3 H 65
chlortetracycline (Aureomycin) H OH CH3 Cl 32
oxytetracycline (Terramycin) OH OH CH3 H 90
demethylchlortetracycline (Declomycin) H OH H Cl 35
doxycycline (Vibramycin) OH CH3 H H 16
minocycline (Minocin) H H H N(CH3) 9

4. Tetracyclines - Uses
Gram- Bacteria
• Helicobacter pylori (duodenal ulcer)
• Borrelia recurrentis (Lyme disease, relapsing fever)
Other Organisms
• Mycoplasma pneumoniae
• acne

5. Tetracycline - Mechanism
• Inhibits protein synthesis
• Static
• Chelates divalent cations -- Ca++
, Mg++

6. Tetracycline - Adverse Effects
• headache, nausea, vomiting
• discoloration of bones and teeth
• photosensitivity
• liver damage
• superinfection

7. Superinfection
A new infection appearing during treatment for a primary
infection
The organism will be resistant to the antibiotic used for the
primary infection
Organisms causing superinfection
Staphylococcus aureus - enterocolitis
Candida albicans - vagina, mouth
Clostridium difficile - pseudomembranous colitis
Risk factors
in hospital > 6 days
6 > age > 60
broad spectrum antibiotic

8. Tetracylines
• Administration
Oral administration but interference by
food, Ca++
, Mg++
• Excretion
renal, fecal enterohepatic

9. Chloramphenicol - structure/features
Features
• Broad Spectrum
• Inexpensive
• Oral administration
• Virtually non-toxic

10. Chloramphenicol - uses/toxicity
Uses
• Haemophilus influenzae (meningitis)
• Typhus
• Rocky Mountain Spotted Fever
• Eye infections
Adverse Effects
• superinfection
• aplastic anemia

11. Chloramphenicol - mechanism
• Inhibits protein synthesis
• Static

13. Macrolides
• Erythromycin is a naturally-occurring macrolide
derived from Streptomyces erythreus – problems
with acid lability, narrow spectrum, poor GI
intolerance, short elimination half-life
• Structural derivatives include clarithromycin and
azithromycin:
 Broader spectrum of activity
 Improved Pharmacokinetic properties – better
bioavailability, better tissue penetration, prolonged half-
lives
 Improved tolerability

14. Macrolides
Mechanism of Action
Inhibits protein synthesis by reversibly binding
to the 50S ribosomal subunit
 Suppression of RNA-dependent protein synthesis
Macrolides typically display bacteriostatic
activity, but may be bactericidal when present
at high concentrations against very susceptible
organisms
Time-dependent activity

15. QUICK REVIEW - Protein Synthesis

16. Macrolide Spectrum of Activity
Gram-Positive Aerobes – erythromycin and
clarithromycin display the best activity
(Clarithro>Erythro>Azithro)
• Methicillin-susceptible Staphylococcus aureus
• Streptococcus pneumoniae (only PSSP) – resistance is
developing
• Group A/B/C/G and viridans streptococci
• Bacillus sp., Corynebacterium sp.

17. Macrolide Spectrum of Activity
Gram-Negative Aerobes – newer macrolides
with enhanced activity
(Azithro>Clarithro>Erythro)
• H. influenzae (not erythro), M. catarrhalis,
Neisseria sp., Campylobacter jejuni, Bordetella
pertussis
• Do NOT have activity against any
Enterobacteriaceae or Pseudomonas

18. Macrolide Spectrum of Activity
Anaerobes – activity against upper airway anaerobes
Atypical Bacteria – all macrolides have excellent
activity against atypical bacteria including:
• Legionella pneumophila - DOC
• Chlamydia sp.
• Mycoplasma sp.
• Ureaplasma urealyticum
Other Bacteria – Mycobacterium avium complex
(MAC – only A and C), Treponema pallidum,
Campylobacter, Borrelia, Bordetella, Brucella.
Pasteurella

19. Macrolides
Pharmacology
Absorption
 Erythromycin – variable absorption (15-45%);
food may decrease the absorption
• Base: destroyed by gastric acid; enteric coated
• Esters and ester salts: more acid stable
 Clarithromycin – acid stable and well-absorbed,
55% bioavailable regardless of presence of food
 Azithromycin –acid stable; 38% bioavailable; food
decreases absorption of capsules

20. Macrolides
Pharmacology
Distribution
 Extensive tissue and cellular distribution – clarithromycin
and azithromycin with extensive penetration
 Minimal CSF penetration
Elimination
 Clarithromycin is the only macrolide partially eliminated by
the kidney (18% of parent and all metabolites); requires
dose adjustment when CrCl < 30 ml/min
 Hepatically eliminated: ALL
 NONE of the macrolides are removed during hemodialysis!
 Variable elimination half-lives (1.4 hours for erythro; 3 to 7
hours for clarithro; 68 hours for azithro)

21. Macrolides
Adverse Effects
• Gastrointestinal – up to 33 %
 Nausea, vomiting, diarrhea, dyspepsia
 Most common with erythro; less with new agents
• Cholestatic hepatitis - rare
 > 1 to 2 weeks of erythromycin estolate
• Thrombophlebitis – IV Erythro and Azithro
 Dilution of dose; slow administration
• Other: ototoxicity (high dose erythro in
patients with RI); QTc prolongation; allergy

22. Macrolides
Drug Interactions
Erythromycin and Clarithromycin ONLY–
are inhibitors of cytochrome p450 system in
the liver; may increase concentrations of:
Theophylline Digoxin, Disopyramide
Carbamazepine Valproic acid
Cyclosporine Terfenadine, Astemizole
Phenytoin Cisapride
Warfarin Ergot alkaloids

23. Vancomycin
Mechanism of Action
• Inhibits bacterial cell wall synthesis at a site
different than beta-lactams
• Inhibits synthesis and assembly of the second
stage of peptidoglycan polymers
• Binds firmly to D-alanyl-D-alanine portion of
cell wall precursors
• Bactericidal (except for Enterococcus)

24. Vancomycin
Spectrum of Activity
Gram-positive bacteria
– Methicillin-Susceptible AND Methicillin-Resistant S.
aureus and coagulase-negative staphylococci
– Streptococcus pneumoniae (including PRSP), viridans
streptococcus, Group A/B/C/G streptococcus
– Enterococcus sp.
– Corynebacterium, Bacillus. Listeria, Actinomyces
– Clostridium sp. (including C. difficile), Peptococcus,
Peptostreptococcus
No activity against gram-negative aerobes or
anaerobes

25. Vancomycin
Pharmacology
• Absorption
– absorption from GI tract is negligible after oral
administration except in patients with intense colitis
– Use IV therapy for treatment of systemic infection
• Distribution
– widely distributed into body tissues and fluids, including
adipose tissue; use TBW for dosing
– inconsistent penetration into CSF, even with inflamed
meninges
• Elimination
– primarily eliminated unchanged by the kidney via
glomerular filtration
– elimination half-life depends on renal function

26. Vancomycin
Clinical Uses
• Infections due to methicillin-resistant staph
including bacteremia, empyema, endocarditis,
peritonitis, pneumonia, skin and soft tissue
infections, osteomyelitis
• Serious gram-positive infections in β-lactam
allergic patients
• Infections caused by multidrug resistant bacteria
• Endocarditis or surgical prophylaxis in select cases
• Oral vancomycin for refractory C. difficile colitis

27. Vancomycin
Adverse Effects
Red-Man Syndrome
– flushing, pruritus, erythematous rash on face and
upper torso
– related to RATE of intravenous infusion; should be
infused over at least 60 minutes
– resolves spontaneously after discontinuation
– may lengthen infusion (over 2 to 3 hours) or
pretreat with antihistamines in some cases

28. Vancomycin
Adverse Effects
• Nephrotoxicity and Ototoxicity
– rare with monotherapy, more common when
administered with other nephro- or ototoxins
– risk factors include renal impairment, prolonged
therapy, high doses, ? high serum concentrations,
other toxic meds
• Dermatologic - rash
• Hematologic - neutropenia and
thrombocytopenia with prolonged therapy
• Thrombophlebitis

29. Linezolid
Mechanism of Action
• Binds to the 50S ribosomal subunit near to
surface interface of 30S subunit – causes
inhibition of 70S initiation complex which
inhibits protein synthesis
• Bacteriostatic (cidal against some bacteria)

30. Linezolid
Spectrum of Activity
Gram-Positive Bacteria
– Methicillin-Susceptible, Methicillin-Resistant AND
Vancomycin-Resistant Staph aureus and coagulase-
negative staphylococci
– Streptococcus pneumoniae (including PRSP), viridans
streptococcus, Group streptococcus
– Enterococcus faecium AND faecalis (including VRE)
– Bacillus. Listeria, Clostridium sp. (except C. difficile),
Peptostreptococcus, P. acnes
Gram-Negative Aerobes – relatively inactive
Atypical Bacteria
– Mycoplasma, Chlamydia, Legionella

31. Linezolid
Pharmacology
• Concentration-independent bactericidal
activity
• Absorption – 100% bioavailable
• Distribution – readily distributes into well-
perfused tissue; CSF penetration ≈ 70%
• Elimination – both renally and nonrenally, but
primarily metabolized; t½ is 4.4 to 5.4 hours;
no adjustment for RI; not removed by HD

32. Linezolid
Adverse Effects
• Gastrointestinal – nausea, vomiting,
diarrhea (6 to 8 %)
• Headache – 6.5%
• Thrombocytopenia – 2 to 4%
– Most often with treatment durations of > 2
weeks
– Therapy should be discontinued – platelet
counts will return to normal

33. Linezolid (Zyvox®)
Drug–Drug/Food interactions
Linezolid is a reversible, nonselective inhibitor of
monoamine oxidase. Tyramine rich foods, adrenergic
drugs and serotonergic drugs should be avoided due to the
potential drug-food and drug-drug interactions. A
significant pressor response has been observed in normal
adult subjects receiving linezolid and tyramine doses of
more than 100 mg. Therefore, patients receiving linezolid
need to avoid consuming large amounts of foods or
beverages with high tyramine content.

34. Linezolid and Tyramine
cont
Foods high in tyramine content include those that may have
undergone protein changes by aging, fermentation,
pickling, or smoking to improve flavor, such as aged
cheeses (0 to 15 mg tyramine per ounce); fermented or air-
dried meats such as pepperoni (0.1 to 8 mg tyramine per
ounce); sauerkraut (8 mg tyramine per 8 ounces); soy
sauce (5 mg tyramine per 1 teaspoon); tap beers (4 mg
tyramine per 12 ounces); red wines (0 to 6
mg tyramine per 8 ounces). The tyramine content of any
protein-rich food may be increased if stored for long
periods or improperly refrigerated.

35. Clindamycin
Mechanism of Action
Inhibits protein synthesis by binding
exclusively to the 50S ribosomal subunit
 Binds in close proximity to macrolides –
competitive inhibition
Clindamycin typically displays bacteriostatic
activity, but may be bactericidal when present
at high concentrations against very susceptible
organisms

36. Clindamycin
Spectrum of Activity
Gram-Positive Aerobes
• Methicillin-susceptible Staphylococcus
aureus (MSSA)
• Methicillin-resistant Staphylococcus
aureus (MRSA) – some isolates
• Streptococcus pneumoniae (only PSSP) –
resistance is developing
• Group and viridans streptococci

37. Clindamycin
Spectrum of Activity
Anaerobes – activity against Above the Diaphragm
Anaerobes (ADA)
Peptostreptococcus some Bacteroides sp
Actinomyces Prevotella sp.
Propionibacterium Fusobacterium
Clostridium sp. (not C. difficile)
Other Bacteria – Toxoplasmosis gondii, Malaria

38. Clindamycin
Pharmacology
Absorption – available IV and PO
 Rapidly and completely absorbed (90%); food with
minimal effect on absorption
Distribution
 Good serum concentrations with PO or IV
 Good tissue penetration including bone; minimal CSF
penetration
Elimination
 Clindamycin primarily metabolized by the liver; half-
life is 2.5 to 3 hours
 Clindamycin is NOT removed during hemodialysis

39. Clindamycin
Adverse Effects
• Gastrointestinal – 3 to 4 %
 Nausea, vomiting, diarrhea, dyspepsia
• C. difficile colitis – one of worst offenders
 Mild to severe diarrhea
 Requires treatment with metronidazole
• Hepatotoxicity - rare
 Elevated transaminases
• Allergy - rare

40. New Guys on the Block
• Tigecycline (Tygacil®)
• Daptomycin (Cubicin®)

41. Tigecycline
Mechanism of Action
Binds to the 30S ribosomal subunit
of susceptible bacteria, inhibiting
protein synthesis.

42. Tigecycline
Spectrum of Activity
Broad spectrum of activity
• Treatment of complicated skin and skin structure
infections caused by susceptible organisms,
including methicillin-resistant Staphylococcus
aureus and vancomycin-sensitive Enterococcus
faecalis; treatment of complicated intra-
abdominal infections

43. Tigecycline
Pharmacokinetics
• Metabolism: Hepatic, via glucuronidation, N-
acetylation, and epimerization to several metabolites,
each <10% of the dose
• Half-life elimination: Single dose: 27 hours;
following multiple doses: 42 hours
• Excretion: Urine (33%; with 22% as unchanged
drug); feces (59%; primarily as unchanged drug) –
No dose adjustment required in renal dysfunction

44. Tigecycline
Adverse Effects
• >10%: Gastrointestinal: Nausea (25% to 30%), diarrhea (13%)
• 2% to 10%:
• Cardiovascular: Hypertension (5%), peripheral edema (3%), hypotension
(2%)
• Central nervous system: Fever (7%), headache (6%), dizziness (4%), pain
(4%), insomnia (2%)
• Dermatologic: Pruritus (3%), rash (2%)
• Endocrine: Hypoproteinemia (5%), hyperglycemia (2%), hypokalemia (2%)
• Hematologic: Thrombocythemia (6%), anemia (4%), leukocytosis (4%)
• Hepatic: SGPT increased (6%), SGOT increased (4%), alkaline phosphatase
increased (4%), amylase increased (3%), bili increased (2%), LDH increased
(4%)
• Neuromuscular & skeletal: Weakness (3%)
• Renal: BUN increased (2%)
• Respiratory: Cough increased (4%), dyspnea (3%)

45. Daptomycin
Mechanism of Action
 Daptomycin binds to components of the cell
membrane of susceptible organisms and causes
rapid depolarization, inhibiting intracellular
synthesis of DNA, RNA, and protein.
 Daptomycin is bactericidal in a concentration-
dependent manner

46. Daptomycin
Spectrum of Activity
Gram-Positive Aerobes
Treatment of complicated skin and skin
structure infections caused by susceptible
aerobic Gram-positive organisms;
• Staphylococcus aureus bacteremia, including right-
sided infective endocarditis caused by MSSA or MRSA

47. Daptomycin
Pharmacokinetics
• Absorption – available IV only
• Half-life elimination: 8-9 hours (up to 28 hours in
renal impairment)
• Excretion: Urine (78%; primarily as unchanged
drug); feces (6%)
• Dosage adjustment in renal impairment:
– Clcr <30 mL/minute: Administer dose q48hr

48. Daptomycin
Adverse Effects
• Hematologic: Anemia (2% to 13%)
• Gastrointestinal:
– Diarrhea (5% to 12%)
– vomiting (3% to 12%)
– constipation (6% to 11%)

49. FDA Categorization of Antibiotics in Pregnancy
• Category A
– Controlled studies in women fail to demonstrate a risk to the fetus in the first trimester (and there is no
evidence of a risk in later trimesters), and the possibility of fetal harm appears remote.
• Category B
– Either animal-reproduction studies have not demonstrated a fetal risk but there are no controlled studies
in pregnant women, or animal-reproduction studies have shown an adverse effect (other than a decrease
in fertility) that was not confirmed in controlled studies in women in the first trimester (and there is no
evidence of a risk in later trimesters).
• Category C
– Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other)
and there are no controlled studies in women, or studies in women and animals are not available. Drugs
should be given only if the potential benefit justifies the potential risk to the fetus.
• Category D
– There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be
acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease
for which safer drugs cannot be used or are ineffective).
• Category X
– Studies in animals or human beings have demonstrated fetal abnormalities, or there is evidence of fetal
risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly
outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.

50. Antibiotics in Pregnancy
FDA Category Antibiotics in Category
A
B Penicillins, Cephalosporins, Carbapenems (except Imipenem),
Daptomycin, Vancomycin (oral), Clindamycin, Erythromycin,
Azithromycin, Metronidazole (avoid first trimester),
Nitrofurantoin, Acyclovir, Amphoterocin B, Ethambutol
C Quinolones, Chloramphenicol, Clarithromycin, Imipenem,
Linezolid, Trimethoprim/Sulfa (D if used near term),
Vancomycin (IV), Rifampin, INH, PZA, PAS, Fluconazole,
Caspofungin
D Tetracyclines (Doxy, Tige, Mino), Voriconazole,
Aminoglycosides (some put gentamicin as a category C)
X Ribavarin

51. Antibiotics Penetration into Eucaryotic Cells (esp.
Macrophages)
Antibiotic Class Intracellular
Accumulation Ratio
Predominant
Subcellular Localization
Beta Lactams <1 Cytosol
Glycopeptides
(Vancomycin)
8 (after 24 hrs) Lysosomes
Oxazolidinones
(linezolid)
1 Unknown
Aminoglycosides 2-4 (after several days) Lysosomes
Macrolides 4-300 Lysosomes/cytosol
Fluoroquinolones 4-10 Cytosol
Clindamycin 5-20 Unknown
Tetracyclines 1-4 Unknown
Antibiotics in bold print are generally considered most
effective for intracellular organisms