Transcript Commonly Encountered Microbes and the Antibacterial Drugs

Commonly Encountered Microbes
and the Antibacterial Drugs used
to treat them
Felix Hernandez, M.D.
Gram Positive Cocci
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Appearance:
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Blue and round by microscopy
Have a thick peptidoglycan cell wall that surrounds the
bacteria
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This wall is impermeable and is responsible for retention of the
blue dye in gram staining
Penicillins, cephalosporins, bacitracin, vancomycin inhibit the
synthesis of the peptidoglycan cell wall
Common sites of invasion:
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Staph aureus and staph epidermidis inhabit most
people’s skin and can infect wounds, surgical sites and
indwelling catheters.
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They may cause infective endocarditis
Streptococous pneumoniae is the cause of community
acquired pneumonia and adult bacterial meningitis
Group A Beta-hemolytic Streptococcus causes strep
throat
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If untreated it can cause an immunologic reaction in the heart
and joints known as rheumatic fever.
Gram Negative Pathogens
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Can be divided into four groups:
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1. enterics  normally inhabit the GI tract
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Ex: E. coli, Shigella, Salmonella, Enterobacter
2. Haemophilus influenzae
3. Neisseria
4. Pseudomonas
Have a thin layer of peptidoglycan that is
surrounded by an outer membrane which is made
of lipopolysacharrides (LPS) which acts as a toxin
Some strains produce B-lactamase which is a
penicillin destroying enzyme that is concentrated in
the space between the outer membrane and cell
wall
Gram Negative Pathogens
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Common sites of invasion:
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Enterics are responsible for UTI and aspiration
pneumonia
Neisseria gonorrhea is responsible for the STD
gonorrhea
Neisseria meningitidis and H. influenzae both
cause meningitis although H. influenzae more
commonly causes pneumonia in the elderly
Pseudomonas aeruginosa is responsible for
hospital acquired infections because if adequate
moisture is available it can colonize any surface
in the hospital and is resistant to many
disinfectants
Anaerobes
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Common organisms include Bacteriodes fragilis, Clostridium
difficile, Clostridium botulinum, and Clostridium tetani
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C. botulinum causes botulism and C. tetani causes tetanus
Metronidazole, chloramphenicol and clindamycin are
effective against anaerobic bacteria
Infections are frequently encased in an abscess wall and
they produce foul smelling gas
They colonize the mouth, GI tract, and skin
Infections develop when they penetrate poorly oxygenated
tissues such as the diabetic foot or normally sterile tissues
like the peritoneum.
With the use of broad spectrum antibiotics, C. difficile
proliferates and releases a toxin that causes
pseudomembranous colitis.
Cell Wall Synthesis
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Peptidoglycan chains are synthesized in the
cytoplasm and get transferred across the
plasma membrane and linked to other
peptidoglycan chains
This results in a chain link that surrounds the
bacteria
Human cells don’t have cell walls so cell wall
synthesis inhibitors don’t have many side
effects
Cell Wall Synthesis Inhibitors
Penicillins
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Penicillin G (IV/IM) and Penicillin V (PO)
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Narrow Spectrum, Penicillinase Sensitive
MOA: inhibit cross linking of cell wall components
DOC for: Staph and Strep, N. meningitidis, C. tetani,
Syphilis
Side Effects: hypersensitivity reactions, neutropenia,
nephrotoxicity
Naficillin
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Narrow Spectrum, Penicillinase Resistant
MOA: has a bulky side group that protects it from
penicillinase
DOC for: penicillinase producing Staph
Side Effects: severe thrombophlebitis and liver toxicity
with elevated LFTs
Cell Wall Synthesis Inhibitors
Penicillins
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Broad Spectrum
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Ampicillin
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MOA: are hydrophilic and can penetrate the porins in Gram –
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DOC for: listeria and enterococcus
Side Effects: Diarrhea
Amoxicillin
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Are not effective against pencillinase producers
MOA: same
DOC for: empiric therapy in otitis media, sinusitis and pneumonia
Side Effects: Diarrhea
Amoxicillin and Clavulanate (Augmentin)
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MOA: same but the clavulanate inhibits penicillinases
DOC for: Moraxella catarrhalis (OM), H. influenza
Side Effects: Diarrhea
Cell Wall Synthesis Inhibitors
Penicillins
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Anti-Pseudomonals
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Ticarcillin
MOA: has a side chain that makes it more resistant to
penicillinases from gram – species
 DOC for: Pseudomonas
 Side Effects: None
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Piperacillin
MOA: same
 DOC for: enterobacteria and gram + cocci
 Side Effects: Neutropenia and hematologic
abnormalities
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Cell Wall Synthesis Inhibitors
Cephalosporins
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First Generation- Narrow Spectrum, sensitive
to B-Lactamase
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Cephalexin (Keflex), Cefazolin (Kefzol)
MOA: Binds penicillin binding proteins and inhibits cell
wall synthesis
 Resistance: bacteria reduce drug permeability, mutate
penicillin binding proteins and produce B-lactamase
 Spectrum: Gram + cocci except for MRSA and some
Gram –, Cefazolin is used in surgical prophylaxis and
for treating skin and soft tissue infections by Staph or
Strep.
 Side Effects: hypersensitivity reaction, GI
disturbances, possible seizures and confusion with
Cefazolin, Nephrotoxicity
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Cephalosporins
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Second Generation- Broader Gram – Activity
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Cefaclor (Ceclor), Cefuroxime (Cefitin), Cefoxitin,
Cefotetan
MOA: same as first gen but resistance to Lactamase
 Spectrum: Gram+ cocci with extended Gram – activity
with H. influenza, Enterobacter, Proteus and Neisseria
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Clinical Uses: otitis media, pharyngitis, sinus, skin and
respiratory infections
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None are effective against pseudomonas
Cefuroxime is used as a single dose therapy for N. gonorrhea
Side Effects: Same as first gen
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Cefaclor is associated with serum sickness (delayed allergic
response)
Cephalosporins
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Third Generation- Broad Spectrum, Resistant
to cephalosporinases
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Ceftriaxone (Rocephin), Ceftazidime, Cefepime
MOA: same as first gen but more resistant to
lactamases
 Spectrum: gram- bacilli, some pseudomonas, gram+
cocci (staph and strep)
 Clinical Uses: penetrate the CSF so can be used for
CNS infections
 Side Effects: same as first gen and acalculous
cholestasis
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Cell Wall Synthesis Inhibitors
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Vancomycin
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MOA: prevents transfer of cell wall precursors from
plasma membrane to cell wall
Clinical Use: DOC for penicillin or methicilliin resistant
staph and strep
Side Effects: thrombophlebitis, ototoxicity, nephrotoxicity,
Red Man Syndrome (IV)  tachy, flushing, parethesias,
hypotension and severe nephrotoxicity
Bacitracin
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MOA: inhibits recycling of the carrier which transports
cell wall precursors across the plasma membrane
Clinical Use: Gram + infections in the skin and eye
Side Effects: severe nephrotoxicity when administered IM
Seen in combo with neomycin in Neosporin
Cell Wall Synthesis Inhibitors
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Carbapenem
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Imipinem/Cilastatin, Meropenem
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MOA: inhibits cross linking of cell wall components
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Cilastatin inhibits renal metabolism of imipinem
Clinical Uses: DOC for Acinetobacter, used to treat
Gram + and – including lactamase producers and
pseudomonas
 Side Effects: hypersensitivity. Doesn’t cause sterile
bowel because of low concentration in the bowel
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Cell Wall Synthesis Inhibitors
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Monobactam
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Aztreonam
MOA: Inhibits cross linking of cell wall components
 Clinical Use: Excellent coverage of Gram – including P.
aeruginosa. Not active against Gram +
 Side Effects: hypersensitivity, seizures, and hepatitis
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Lipopeptides
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Daptomycin
MOA: Depolarizes bacterial cell membrane
 Clinical Uses: skin infections caused by S. aureus,
MRSA and Strep
 Side Effects: Hepatotoxicity, diarrhea, and rash
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DNA Inhibitors
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Quinolones
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Nalidixic Acid (NegGram)
MOA: blocks a subunit of DNA gyrase therefore
preventing supercoiling and inhibiting DNA synthesis
 Clinical Uses: enteric Gram – but not Pseudomonas
 Side Effects: hypersensitivity rxn, photosensitivity,
seizure, HA.
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Displaces oral anticoagulants from plasma proteins
Causes growth plate arrest so not used in children
DNA Inhibitors
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Fluroquinolones
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Norfloxacin
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Ciprofloxacin (Cipro)
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MOA: inhibits DNA gyrase and topoisomerase activity
Clinical Uses: good gram – coverage
Side Effects: cartilage damaged so children is a CI
MOA: same as above
Clinical Uses: excellent Gram – coverage with some Gram +
Side Effects: Same as above
Levofloxacin (Levaquin)
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MOA: Same as above
Clinical Uses: excellent gram – coverage and improved Staph.
Coverage, treat legionella and chlamydia atypical pneumonia
Side Effects: same as above
DNA Inhibitors
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Metronidazole (Flagyl)
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MOA: enters the bacteria and is activated by reduction of
the nitro group. Binds DNA and inhibits its synthesis
Clinical Uses: Bacteriodes, Clostridium and Protozoans
such as E. histolytica, Trichomonas, and Giardia
Side Effects: Disulfiram-like reaction with alcohol
(flushing, vomiting and headache), CNS disturbance,
bloating and cramping
Nitrofurantoin (Macrodantin)
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MOA: mechanism unclear but may damage DNA
Clinical Uses: kills many urinary pathogens but not
pseudomonas
Side Effects: hepatotoxicity, pulmonary fibrosis,
neuropathy
Antimetabolites
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Sulfonamides
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Sulfadiazine
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MOA: structurally similar to para-amino benzoic acid (PABA) and
compete with it and prevent it from being incorporated into
folate so you block DNA, RNA or protein synthesis
Clinical Uses: both gram + and -, used to treat uncomplicated
UTI, chancroid, and prophylaxis against rheumatic fever
Side Effects: bone marrow depression, renal toxicity,
photosensitivity, hemolysis, Steven-Johnson syndrome (serum
sickness), Kernicterus (compete with bilirubin for albumin sites
resulting in bilirubin deposited in brain nuclei)
Trimethoprim/Sulfamethoxazole (TMP/SMZ,
Cotrimoxazole, Septra, Bactrim)
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MOA: same as above plus prevents reduction of dihydrofolate to
tetrahydrofolate by inhibiting dihydrofolate reductase
Clinical Uses: enteric gram -, Salmonella, effective for UTI, acute
otitis media and traveler’s diarrhea, used for PCP prophylaxis in
immunocompromised
Side Effects: same as above
Protein Synthesis Inhibitors
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Aminoglycosides (bacteriocidal)
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Gentamycin, Streptomycin, Tobramycin
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MOA: bind at the 30s/50s subunit interface and results in
abnormal reading of mRNA and defective protein synthesis
Resistance: mutation of binding sites, inhibition of transport and
permeability of the drugs
Clinical Uses: aerobic and faculative gram – bacilli, anaerobic
bacteria are resistant because transport into the organism is
oxygen dependent
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DOC for E.coli, Proteus and Pseudomonas
Side Effects: nephrotoxicity (high troughs) and ototoxicity (high
peaks)
Amikacin
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MOA is the same as above but it has a different resistance profile
so it is reserved for use in Gram – infections that are resistant to
other aminoglycosides
Protein Synthesis Inhibitors
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Chloramphenicol
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MOA: reversibly binds to the 50s subunit and prevents
the tRNA from associating with peptidyl transferase
Resistance: Acetyl transferases inactivate the drugs
Clinical Uses: excellent coverage of most gram+ and
gram – including anaerobes.
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DOC for typhoid fever, H. flu meningitis or epiglottitis
Side Effects: reversible bone marrow suppression,
aplastic anemia, gray baby syndrome (in newborns
abdominal distention, vomiting, cyanosis, hypothermia,
collapse and death (40%)
Linezolid (Zyvox)
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MOA: binds to 50s subunit
Clinical Uses: vancomycin resistant gram +
Side Effects: None
Protein Synthesis Inhibitors
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Macrolides
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Erythromycin
MOA: prevents translocation of polypeptide chain by
binding the P site of the 50s subunit
 Resistance: mutation of binding site by methylation
 Clinical Uses: bacteria lacking cell walls (mycoplasma,
legionella and chlamydia), gram + aerobes, gram –
aerobes except campylobacter and H. flu. Poor
anaerobic coverage
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DOC for Mycoplasma pneumonia, neonate with chlamydia
pneumonia, pertusis
Side Effects: GI upset, injections are painful due to
venodestruction
Protein Synthesis Inhibitors
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Clarithromycin (Biaxin)
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MOA: same
Resistance: same
Clinical Uses: Mycobacterium avium, Strep throat and
URI and some anaerobes
Side Effects: GI upset and headache but less frequently
than Erythromycin
Azithromycin (Zithromax)
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MOA: same
Resistance: same
Clinical Uses: combined erythro and clarithro. Used to
treat same things and also uncomplicated chlamydia
Side Effects: GI upset and abdominal pain but less
frequently than erythro
Protein Synthesis Inhibitors
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Lincosamides
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Clindamycin (Celocin)
MOA: binds to the 50s subunit and prevents chain
elongation by blocking transpeptidation
 Resistance: alteration of ribosome binding site and
enzymatic inactivation of the drug
 Clinical Uses: covers gram + and most anaerobes.
DOC for severe anaerobic GI infections
 Side Effects: abdominal cramps, diarrhea, reversible
LFT elevation, classically associated with
pseudomembranous colitis (due to C. diff resistance)
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Protein Synthesis Inhibitors
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Tetracycline, Doxycycline
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MOA: Inhibits protein synthesis by binding to the
30s subunit and blocking amino-acid linked tRNA
from binding to the A site of the ribosome
Resistance: proteins that transport drugs out of
the cell
Clinical Uses: acne and chlamydia. Also used for
Borrelia Burgdorferi (Lyme Disease)
Side Effects: GI distress, reversible
nephrotoxicity, hepatotoxicity, photosensitivity,
dental staining (gray line)