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Drug List (Sulfonamides)
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Protype/Important
sulfisoxazole
sulfamethoxazole
sulfadiazine
trimethoprimsulfamethoxazole
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Others
Sulfasalazine
silver sulfadiazine
sulfacetamide
sulfadoxinepyrimethamine
• triple-sulfonamides
Drug List (Penicillins)
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Prototype/Important
Pen G (natural pen)
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Nafcillin (Penase resis.) •
Ampicillin (aminopen.) •
Piperacillin (antipseud.) •
•
Related Drugs
Others
Pen G procaine
Pen G benzathine
Pen V
Methacillin, oxacillin
Amoxacillin
Ticarcillin
Clavulanic acid,
sulbactam (beta
lactamase inhibitors)
Drug List (Cephalosporins)
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Prototype/Important •
Cefazolin (1st gen.)
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Cefuroxime (2nd gen.) •
Cefotaxime (3rd gen.) •
Cefepine (4th gen.)
•
Others
Cephalexin (oral, 1st gen.)
Cefaclor (oral, 2nd gen.)
Cefixime (oral, 3rd gen.)
Ceftriaxone (long duration,
3rd gen.)
Cephalosporins (half-life)
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Cefazolin (1.5-2hr)
Cefuroxime (1.3 hr)
Cefotaxime (1 hr)
Cefepine (1 hr)
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•
•
Cephalexin (1 hr)
Cefaclor (0.75 hr)
Cefixime (3-4 hr)
Ceftriaxone (6-8 hr)
Drug List (other beta lactams)
• Prototype
• Imipenem
• Others
• Imipenem-cilistatin
Drug List (aminoglycosides)
• Prototype
• Gentamicin
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Others
Amikacin
Streptomycin
Neomycin
Drug List (antitubercular)
• Important
• Isoniazid
• Rifampin
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•
•
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Others
Streptomycin
Ethambutol
Pyrazinamide
Drug List
tetracyclines/chloramphen.
• Prototype
• Tetracycline
• Chloramphenicol
• Others
• Doxycycline
• Minocycline
Drug List (agents for UTI)
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Prototype/Important
Methenamine
Ciprofloxacin
• Related agents
• Phenazopyridine
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Others
Nitrofurantoin
Norfloxacin (only UTI)
Ofloxacin, Levofloxacin
Moxifloxacin,
Sparfloxacin,
Trovofloxacin (newer
expanded spectrum)
Drug List (miscellaneous)
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•
•
•
•
Prototype
Erythromycin
Clindamycin
Vancomycin
Metronidazole
• Others
• Azithromycin
Penicillin Subclasses
Pen G
Nafcillin
Ampicillin
Amoxacillin
Ticarcillin
Piperacillin
Resistant to No
beta
lactamases
Clinical
status
Yes(gram pos.) No
Spectrum
Strep.
N.men.
Staph.
(penicillinaseproducing)
same as
Pseud.aerug., some
pen G plus enteric gram neg.
H.flu.,
bacilli
E.coli
Combined
with beta
lactamase
inhibitors
No
No
Yes
No
Yes
Clinical Status of Penicillins
• Pen G & V: Group A Strep., most Strep.
pneumoniae, N. meningitidis, T. pallidum
(syphilis)
• Nafcillin: penicillinase-producing Staph.
• Ampicillin/Amoxacillin: H.flu. (otitis media,
URTI), E.coli (UTI), Shigella, Salmonella
• Piperacillin: Pseud. aerug. (UTI), some gram
neg. bacilli
Cephalosporin Subclasses
First Gen. Second Gen. Third Gen.
(Cefazolin) (Cefuroxime) (Cefotaxime)
Spectrum
Resistance
to beta
lactamases
Clinical
status
CNS
penetranc
e
same as Pen G
plus Staph.
more gram neg.
Klebsiella
Relatively
resistant to
gram pos.
inadequate
Expanded gram
neg. and H. flu.
Good gram neg.
bacilli (hospitalacquired)
Increased vs.
gram neg.
More resistant to
gram neg.
inadequate for
most
adequate
Clinical Status of
Cephalosporins
• Cefazolin: serious Klebsiella pneumoniae, alternate
to penicillins for strep. & staph.; prophylaxis in
surgery vs. staph & enteric gram neg.
• Cefuroxime: gram neg. hosp. infections resistant to
1st gen. ceph., including beta lactamase-producing
strains, H.flu. (Cefaclor used orally for some H. flu.)
• Cefotaxime: serious gram neg. bacilli esp. if
meningitis, beta lactamase-producing gonococci
(ceftriaxone preferred); may be combined with AG;
some other 3rd gen. ceph. useful vs. Pseud.aerug.
(ceftazidime)
What are the major differences between
imipenem, penicillins and cephalosporins ?
• Spectrum
• Distribution
– Why is it combined with cilistatin?
• Toxicity
• Clinical Status
Major Differences in
Imipenem, Penicillins, Ceph.
• Spectrum
– Imipenem broadest covers most gram neg. bacilli
(very resistant to beta lactamases) Staph., plus
anaerobes (B. fragilis)
• Pharmacokinetics
– Imipenem metabolized by renal
dehydropeptidases (need cilistatin)
• Toxicity (Imipenem)
– allergic responses, superinfections,
thrombophlebitis, seizures (rare)
Major features of Penicillins
• Spectrum
– Pen G best for strep. but not cover staph.
– Ampicillin for strep., H. flu., salmonella/shigella,
E. coli
• Pharmacokinetics
– eliminated by renal secretion
• Toxicity
– allergic rxs, seizures in high doses
– Ampicillin: rash, diarrhea (superinfections)
– Piperacillin: platelet dysfunction, thromophlebitis
Major Features of
Cephalosporins
• Spectrum
– 1st gen.: strep., staph., more gram neg.bacilli
– 2nd gen.: more gram neg. in hospital, H. flu.
– 3rd gen.: best vs. gram neg. bacilli (very resistant
to beta lactamases)
• Pharmacokinetics
– eliminated by renal secretion (some metabolized)
• Toxicity
– allergic rxs, superinfections, low potential renal
toxicity
What are the unique features
of aztreonam?
• Compared with penicillins and
cephalosporins
– Spectrum
– Pharmacokinetics
– Adverse effects
» Is there cross-sensitivity with penicillins?
Unique Features of
Aztreonam
• Monobactam with only gram neg. spectrum
• no cross allergenicity with pen or ceph
• used alone only for UTI
• potential gram pos. superinfections
• must be given parenterally
What are the important characteristics that
all aminoglycosides have in common?
• Spectrum
• Pharmacokinetics
• Adverse effects
Features of Aminoglycosides
• excellent vs. aerobic gram neg. bacilli
• limited distribution to extracellular fluids
• eliminated almost entirely by glomerular
filtration (monitor renal function)
• serious toxicities
– irreversible ototoxicity
– vestibular toxicity
– nephrotoxicity
– neuromuscular blockade
Summarize the status of aminoglycosides
and third generation cephalosporins
• Clinical status of aminoglycosides
• Clinical status of third generation
cephalosporins
• Clinical status of imipenem
Aminoglycosides vs 3rd Gen.
Cephalosporins/Imipenem
• 3rd gen ceph.: preferred vs. gram neg. sepsis
to avoid serious toxicities of AG
• some 3rd gen. ceph. better vs. Pseud. while
other better vs. other gram neg. bacilli
• initial therapy of life-threatening sepsis
involves combination of AG plus either 3rd
gen. ceph. / antipseudomonal pen/ imipenem
• imipenem reserved for mixed infections that
my involve anerobes (B. fragilis)
Erythromycin
• Clinical use
• Adverse reactions
Erythromycin
• Clinical Uses
• Respiratory infections (Chlamydia,
Mycoplasma, Legionella, Bordetella)
• Alternate to pen in mild-moderate
infect.(strep., H. flu.)
• Adverse effects
– frequent GI disturbances
– cholestatic hepatitis with estolate ester in adults
– inhibition of hepatic CYP3A (drug interactions)
Tetracyclines
• Clinical use
• Adverse reactions
Tetracyclines
• Clinical use
– some gram neg. infections
– Rickettsia, Chlamydia, Mycoplasma
– spirochetes, Lyme disease, acne, travelers diarrhea
• Adverse reactions (numerous)
– discolor teeth in children, phototoxicity, GI
disturbances, superinfections
– vestibular toxicity (minocycline)
– renal toxicity (if renal insufficiency, outdated
tetracyclines
– hepatic toxicity (high doses in malnourished, pregnancy,
liver disease)
Ciprofloxacin
• Clinical use
• Adverse reactions
Ciprofloxacin
• Clinical use
– oral or IV for variety of gram neg. enteric bacilli
– good for UTI; some used for genital infections
due to chlamydia or gonococci
– some used for respiratory tract infections due to
Mycoplasma, Legionella, Brucella, Mycobacteria
– newer analogs better vs. Strep. Pneumoniae
Ciprofloxacin
• Adverse reactions
– some GI
– rash
– cartilage damage in children, tendon ruptures
– photosensitivity
– CNS toxicity (dizziness, ataxia, insomnia)
– seizures (rare)
– Hepatotoxicity only with Trovafloxacin
– Photosensitivity most frequent with
sparfloxacin
Chloramphenicol
• Clinical use
• Adverse reactions
Chloramphenicol
• Clinical use
– alternate for meningitis due to H.flu., N.
meningitidis, Strep. pneumoniae
– severe anaerobic infections of CNS
– alternate to tetracyclines for rickettsia, chlamydia,
brucellosis
• Adverse reactions
– aplastic anemia (rare), bone marrow suppression
(reversible), superinfections, Gray Baby syndrome
Sulfamethoxazole-Trimethoprim
• Clinical use
• Adverse reactions
Trimethoprim-Sulfamethoxazole
• Clinical use
– UTI due to susceptible gram neg. bacilli
– otitis media or chronic bronchitis due to H. flu.,
Strep. pneumoniae
– Pneumocystis carinii
– Salmonella, Shigella, toxigenic E. coli
Trimethoprim-Sulfamethoxazole
• Adverse reactions
– Hematopoietic disorders: anemias (give folinic
acid)
– Hypersensitivity Reactions: frequent allergic
reactions to sulfonamides (rash photosensitivity),
– CNS toxicity (headache, depression,
hallucinations)
– higher incidence side effects in AIDS (fever, rash,
leukopenia, diarrhea)
What drugs are useful in treating anaerobic
infections caused by B. fragilis?
• List five examples
Drugs are useful in treating anaerobic
infections caused by B. fragilis
• Clindamycin
• Chloramphenicol
• Metronidazole
• Imipenem
• Some 2nd gen. cephalosporins
– cefoxitin, cefotetan
– some 3rd gen. cephalosporins and
antipseudomonal penicillins have moderate
activity
What advantages do these drugs have
compared to others within the same class?
• Azithromycin (Zithromax)
• Ceftriaxone (Rocephin)
• Doxycycline (Vibramycin)
• Levofloxacin (Levequin)
Advantages of Azithromycin
• Improved spectrum vs. erythromycin
– especially vs. Mycobacterium avium complex, H.
influenzae, Chlamydiae, some gram neg.
• Long half-life due to accumulation in
macrophages and fibroblasts (5 day regimen
for respiratory tract infections)
• Not inhibit liver CYP metabolism of other
drugs
Advantages of Ceftriaxone
• Increased activity vs. gram-neg. bacilli, esp.
in treating meningitis
• Highly resistant to beta lactamases esp.
Neisseria gonorrheaea and H. influenzae
• Long half-life, used as single dose regimen
for gonorrhea
Advantages of Doxycycline
• Complete oral absorption, not affected by
food or antacids
• Not require dose reduction for patients with
reduced renal function
• Often used for traveler’s diarrhea since better
oral absorption and less GI disturbances
Advantages of Levofloxacin
(Moxifloxacin)
• expanded spectrum vs. some gram pos.
esp. Strep. pneumoniae
• also reliable vs. other resp. tract
pathogens such as chlamydia,
mycoplasma , Legionella, H. influenzae
• good vs. gram neg. causes of UTIs and
gastroenteritis
Case #1
• Trauma accident with severe burn
patient
• Pseud. aerug. pneumonia
• start with cefotaxime (3rd gen. ceph.)
• infection worsened
• patient finally dies of intracerebral
hemorrhage
Case #1 Questions
• 1. Why may a third generation cephalosporin
be a poor choice?
• 2. What complications of some third
generation cephalosporins make them a
particularly bad choice on the basis of the
patient’s risk factors?
• What classes of antimicrobial drugs are
reasonable choices for treating infections
caused by Pseudomonas aeruginosa? List the
notable limitations of each drug class.
Case # 1(Answers)
• 1. cefotaxime not highly effective vs. Pseudomonas
esp. in burn unit as resistance with single drug
therapy
• (use antipsuedomonal pen plus AG)
• 2. some third gen. ceph. cause bleeding
(hypoprothrombinemia) and impair phagocytosis
(pneumonia can worsen, resist.)
• 3. alternatives: piperacillin (platelet dysfunction,
hypersensitivity) plus amikacin (nephrotoxicity,
ototoxicity), or 3rd gen. ceph.(ceftazidime), or
imipenem or fluoroquinolone)
Case #2
• Otitis media initially that developes into
meningitis due to Strep. pneum.
• Given Cefaclor (oral 2nd gen. ceph.) as out
patient
• patient worsens to comatose state and given
massive doses of penicillin and has status
epilepticus
• regains consciousness upon decreasing dose
of penicillin
Case #2 Questions
• 1. Was an oral, “second generation
cephalosporin the best antimicrobial
considering the most likely organism(s) to be
causing his otitis media?
• 2. What feature of penicillin makes it
dangerous in very high doses in patients with
a more permeable blood-brain barrier?
• 3. What alternative antimicrobials may be
recommended in the treatment of meningitis
caused by Streptococcus pneumoniae?
Case #2 (answers)
• 1. 2nd gen. ceph. orally may be inadequate
dose to prevent meningitis; parenteral dose
preferred or high doses of amoxacillin or
penicillin but pt compliance a concern; could
use amoxacillin-clavulanic acid to cover beta
lactamase producing strains
• 2. pen G in high doses causes convulsions
esp. if inflammed meninges
• 3. alternatives: IV pen G or ampicillin,
cefotaxime, or chloramphenicol
Case #3
• Cefuroxime (2nd gen. ceph.) induces
antibiotic associated colitis with severe
diarrhea leading to death
Case #3 Questions
• 1. What disease entities are associated with the
administration of broad-spectrum
antimicrobials?
• 2. Are these complications of broad-spectrum
antimicrobials ever lethal? If so, by what
means?
• 3. What antimicrobial, if any, is recommended
to treat the probable cause of diarrhea in this
patient?
Case #3 (answers)
• 1. overgrowth or superinfection from
exotoxin-producing Clostridium
difficile, staph. or candida
• 2. exotoxin-producing C. difficile may
produce fatalities
• 3. oral vancomycin or metronidazole
Case #4
• UTI in 22 year old woman with gram
neg. bacteria and PMNs in urine
Case #4 Questions
• 1. What is the most likely organism to be
causing her UTI?
• 2. What organism must be excluded as a
possible cause of her pyuria to avoid infection
of the upper genital tract that might leave her
infertile or with an ectopic pregnancy?
• 3. Assume that the gram-neg. bacteria are
bacilli. On the basis of the most likely
organism, what antimicrobials are candidates
for being the best to treat her UTI?
Case #4 Questions (cont.)
• 4. If she were a patient in the Burn Unit who
had developed a UTI, on the basis of the most
likely organism, what antimicrobials would be
likely to be effective in her management?
• 5. How would your management of a UTI
differ if you knew she was just recovering from
profound renal failure associated with recent
trauma?
• 6. If she were pregnant, how would treat the
UTI? Explain your selections/nonselections.
Case #4 (answers)
• 1. E.coli, other gram neg. bacilli
• 2. exclude gonococcal urethritis
• 3. sulfisoxazole, ampicillin/amoxacillin, TMP/SMX,
tetracycline, norfloxacin
• 4. in burn unit cover resistant strains of gram neg.
bacilli; use TMP/SMX or norfloxacin/other fluoroq.
• 5. avoid sulfonamide & AG if poor renal function;
use amoxacillin, doxycycline, or fluoroquinolone
• 6. if pregnant avoid sulfonamides, tetracycline,
fluoroquinolone; consider amoxacillin alone or
with clavulanic acid
Case #5
• Pneumonia due to Pseudomonas
aeruginosa after surgery for crush
injury to chest and arm
• Therapy with aminoglycoside plus
piperacillin
• serum creatinine becomes elevated
Case #5 Questions
• 1. Outline the options available to the surgical
management team and evaluate them.
• 2. What types of patients tend to be
predisposed to aminoglycoside toxicities?
Case # 5 ( answers)
• 1. order serum levels of AG; delay next dose
by 4-8 hours; change from AG to
antipseudomonal 3rd gen. ceph. (ceftazidime)
or fluoroquinolone or aztreonam
• 2. pts predisposed to AG toxicity: low GFR,
elderly, dehydration or volume depleted,
prior AG rx, or other nephrotoxic drugs