Sunday, March 16, 2008

Antibiotics - internet search - general guide

ANTIBIOTICS



Overview:

* Antibiotics may need dosage adjustment in patients with renal impairment.
* Calculate creatinine clearance and % of normal dose to be used
by the following formula:
(140-age) (weight in kg)
for men, (x0.85 for women)
(72)(serum creatinine)



* Note: Some abx do not need adjustement for patients with renal
insufficiency (e.g., amphotericin B, azithromycin, ceftriaxone,
chloramphenicol, clindamycin, doxycycline, nafcillin, pyrimethamine,
rifambutin).


PENICILLINS:



1. a) Natural penicillins:
Pen G and V indicated against streptococci, anaerobes (above
the diaphragm), syphilis, Listeria monocytogenes (high dose), dog and
cat bites (Pasteurella multocida ). Does not cover S. aureus.

b) Penicillinase-Resistant Penicillins (PRSP):
Methicillin / nafcillin / oxacillin / dicloxacillin are
indicated against penicillinase producing aureus (MSSA not MRSA) for
endocarditis, osteo.

2. Aminopenicillins:
* Ampicillin / Amoxicillin: G(+) coverage similar to above,
covers many G(-) in GI tract (Salmonella, Shigella, E. coli,
Proteus), N. meningitidis, 70% of H. influenza, Listeria, Nocardia.

* Amoxicillin + clavulanate = Augmentin. Covers most G(+)
except MRSA, and many G (-). Anaerobe coverage similar to group III.
Given PO.

* Ampicillin + sulbactam = Unasyn. Coverage to G(+) similar
to above and G(-) all except Serratia, Enterobacter, Pseudomonas,
Legionella. Anaerobe coverage as group III. Indication: GYN, GI and
skin.

3. Antipseudomonal penicillins:
* CarboxyPCN (carbenicillin and ticarcillin) and ureidoPCN
(mezlocillin =Mezlin(R) and piperacillin = Pipracil(R)) cover most
streptococci, and most G(-) with variable coverage for Klebsiella, M.
catarrhalis, Serratia, Legionella. No coverage for Staphylococcus
(except Timentin(R) and Zosyn(R)). Good anaerobic coverage (B.
fragilis, C. difficile ). Main indication is Pseudomonas aeuroginosa.

* Ticarcillin + clavulanate = Timentin(R). Covers G(+)
similar to Augmentin(R) and all G(-) except Legionella. Anaerobic
coverage like group III (B. fragilis, C. difficile).
9
* Piperacillin + tazobactam = Zosyn(R). Similar to
Timentin(R). Note that for serious Pseudomonas infections an
aminoglycoside should be added for synergism.





CEPHALOSPORINS:



* The cross reactivity with PCN (5-10%) is a concern especially
if pt had anaphylaxis. In that case cephalosporins should be
completely avoided.
* Cephalosporins do not cover Listeria or Enterococcus.

1ST GENERATION

* Cephalexin (Keflex), Cefazolin (Ancef). They cover all
streptococci, S. aureus (not MRSA) and S. epidermis. Among G (-) they
cover N. gonorrhea, M. catarrhalis, H. influenza , E. coli,
Klebsiella. Main indications are surgical prophylaxis and Strep. /
Staph. (not MRSA)



2ND GENERATION

* can be further subdivided into "good for H. influenza"
-cefamandole (Mandol), cefuroxime (Ceftin, Zinacef) and "good for
anaerobes" -cefoxitin (Mefoxin), cefotetan (Cefotan). Similar G(+)
coverage as 1ST generation and better G(-) coverage including N.
meningitis (not the drug of choice for meningitis), Salmonella /
Shigella / Proteus and +/- Yersenia. Cefoxitin and cefotetan will
cover anaerobes below the diaphragm including B. fragilis and
Clostridium (not difficile) and are an excellent choice for GI
surgical procedures.

* Cefamandole & cefotetan interfere with vit. K and may produce
coagulopathy. Also rare disulfiram-like reactions have been
documented. Main indications are GI (colorectal surgery and
appendectomy), and Ob-Gyn procedures.



3RD GENERATION

* Ceftriaxone
(Rocephin) & ceftazidime (Fortaz) are the two most commonly
used IV preparations. G(+) coverage is similar to 1ST and 2ND
generation. Ceftriaxone is indicated for the treatment of meningitis
since it has activity against H. influenza (resistant to PCN),
* N. gonorrhea and N. meningitidis and has good CSF penetration.
Ceftriaxone 125mg IM x1 dose is also used for the treatment of
gonorrhea.

* Ceftazidime is indicated against Pseudomonas. Anaerobic
coverage varies from one drug to the other. G(-) are generally
covered well except for atypicals (e.g. Legionella). Cefixime
(Suprax) and cefpodoxime (Vantin) are the only 3RD generation used PO.
Cefpodoxime has moderate G(+) activity, while that of cefixime is
poor. Both have been approved for the PO treatment of N. gonorrhea.
Older 3RD generation include cefotaxime (Claforan), similar to
ceftriaxone, and cefoperazone (Cefobid), similar to ceftazidime.



4TH GENERATION

* include Cefepime (Maxipine) which is similar to 3rd generation
but with better G(-) coverage (P. aeruginosa, Enterobacter, Serratia,
C. freundii) and better G(+) coverage (S. aureus ).



CARBAPENEMS:

o Most common is imipenam + cilastatin (Primaxin), a wide
spectrum abx which covers most G (+) except MRSA and most G (-) except
Legionella and some strains of Pseudomonas (maltophilia, cepacia ).
It also covers all anaerobes and has activity against Listeria and
Nocardia. It is generally given with cilastatin to inhibit renal
breakdown. Seizures are reported particularly in patients with
history of seizures or renal failure. Main indication is multidrug
resistant bacteria and should not be a first choice.


VANCOMYCIN:

* Covers all G(+) including MRSA, C. difficile, Diphtheria,
Enterococcus. Indications: alternative to PCN / Cephalosporin in the
allergic patient, C. difficile (oral preparation) and MRSA. Red-man
syndrome is seen following rapid administration and is believed to be
histamine mediated. Vancomycin has good CSF penetration and is used
as a secondary drug in meningitis to cover resistant Streptococcus.
Because of emerging patterns in drug resistance, Vancomycin should be
reserved for specific situations and not be used as a first line
agent.



AMINOGLYCOSIDES:



* Gentamycin, tobramycin
and amikacin are the most common. Be aware that all
aminoglycosides have the potential to cause nephrotoxicity and
ototoxicity.
* They cover many G(-) including Pseudomonas aeruginosa (but not
cepacia or maltophilia) and they do not cover Neisseria (gonorrhea or
meningitidis).

* They also do not cover anaerobes, Legionella or atypicals. The
G(+) coverage is poor, but they will cover S. aureus (MSSA only) and
Listeria monocytogenes.

* As volume of distribution increases (CHF, ascites, third
spacing) the dosage of the drug must be increased. There is no CSF
penetration. Peaks and troughs should be measured, although other
dosing alternatives are now being used, such as once-daily 7 mg/kg/day
of gentamycin.

* Main indication is for G(-) sepsis, endocarditis (in combination
with PCN), and for synergism against P. aeruginosa infections.
Spectinomycin is still used in PCN allergic patients as a 2 gm IM x 1
dose for the treatment of gonococcal infections.



TETRACYCLINES:



* Tetracycline, doxycycline, minocycline
- indication today is limited to Rickettsiae, Chlamydia,
Nocardia, Lyme's disease (early), and patients allergic to PCN that
requires treatment for syphilis and P. multocida. Minocycline is more
effective against staph and used for the treatment of acne.
* These drugs should be taken on empty stomach since milk, Fe,
Ca and antacids interfere with absorption. Photosensitivity reported.
Not given to pregnant women or children < 10 years old.



MACROLIDES:



* Until the 1990's, erythromycin was the primary representative of
the macrolide class of antibiotics. In 1991, clarithromycin (Biaxin)
and azithromycin (Zithromax(R)) were approved by the FDA, offering and
expanded antimicrobial spectrum, a lower potential for
gastrointestinal effects, and less frequent dosing relative to
erythromycin.

* Clarithromycin and azithromycin have similar antimicrobial
profiles, providing enhanced activity against H. influenza as compared
with erythromycin and retaining good efficacy against G+ organisms.
They cover Streptococcus, Staphylococcus (not MRSA), +/- N. gonorrhea,
H. influenza, M. catarrhalis, Legionella, M. pneumonia and Chlamydia.
Cross-resistance is seen among all macrolides, particularly in Gram
positive bacteria. Because azithromycin has the best activity against
Chlamydia trachomatis, it has been approved as a 1 gm PO single dose
for the treatment of nongonococcal urethritis and cervicitis.

* More recently, dirithromycin (Dynabac(R)) was added to this
group of antimicrobials. Approved in June 1995, it offers a spectrum
of activity and a safety profile similar to those of erythromycin but
with the advantage of once-daily dosing. Like erythromycin,
dirithromycin has good activity against G+ organisms, but some strains
of H. influenza are resistant. Dirithromycin is also less active than
other macrolides against Legionella species, Chlamydia trachomatis,
and Helicobacter pylori.

* Their main indications are as an alternative to PCN in allergic
patients, non-gonococcal urethritis / cervicitis, URI and pneumonia
secondary to Legionella or Mycoplasma.

* Adverse effects most commonly include gastrointestinal
complaints, particularly nausea, abdominal pain and diarrhea.
Azithromycin and clarithromycin have the lowest incidence of these
effects. Other adverse effects are headache, abnormal LFT's and
(rarely) reversible hearing loss. Clarithromycin can cause a taste
disturbance that may be intolerable for some patients. Achiles
rupture was reported with the latter.
* Drug interactions
are more significant with clarithromycin and erythromycin, as
they both increase serum concentrations of drugs metabolized by the
P-450 system in the liver. They may increase the levels of warfarin,
digoxin, carbamezapine and cause arrhythmias when used with some
antihistamines.



FLUOROQUINOLONES:



* Ciprofloxacin
has good activity against G(-) such as Proteus mirabilis and E.
coli. It is also good for GI pathogens such as Vibrio cholera,
Campylobacter jejuni, Yersinia, Salmonella and Shigella and it is the
drug of choice for traveler's diarrhea. It is the most active
fluoroquinolone against the Pseudomonas species. It is also good
against bacteria that depend on the production of beta lactamase for
survival, thus it covers H. influenza and S. aureus . However, it is
surprisingly weak against streptococci (including S. pyogenes and S.
pneumonia) and it has no activity against anaerobic bacteria,
including B. fragilis. Because of this lack of activity against
anaerobes and weakness against chlamydia and enterococci, it is not a
good choice for the treatment of PID. It has been shown to impair
proper growth of cartilage, and thus cannot be used in children.
* Norfloxacin is similar to ciprofloxacin but it is poorly
absorbed PO. It is concentrated in the GI/GU system and is thus
limited in use for traveler's diarrhea and urine infections.

* Ofloxacin (Floxin) is also very similar to ciprofloxacin, but it
has better activity against Chlamydia and can thus be used to treat
STD's such as Chlamydia (300mg po bid x7days) and gonorrhea (400mg po
single dose) and has been approved as oral monotherapy for treatment
of PID. Like ciprofloxacin it is not very good for streptococci,
staphylococci or enterococci. It can cause hyper or hypoglycemia
particularly in diabetics.

* Levofloxacin (Levaquin) is the pure L-isomer of ofloxacin. It
has better activity against Gram (+) cocci and perhaps less toxicity.
The main advantage is that it is given only once a day (250-500mg po
qd), but it is more expensive than ofloxacin.

* Sparfloxacin (Zagam) is similar to levofloxacin with even better
activity against Gram + cocci (including enterococci), and retaining
good activity against Chlamydia. There is, however, a significant
incidence of drug related phototoxicity (not prevented by the use of
sunscreens), and Torsade de pointes on patients receiving drugs known
to prolong the QT interval.

* Trovafloxacin (Trovan) is active against G(+) bacteria,
including penicillin-susceptible and penicillin-resistant pneumococci;
S. aureus (but not MRSA); anaerobes such as Bacteroides fragilis ;
G(-) bacteria including Pseudomonas aeruginosa; and atypical
organisms including Mycoplasma pneumoniae, Chlamydia trachomatis and
Legionella species. Unfortunately it is used infrequently due to
potential liver toxicity.

* Grepafloxacin has G(+) activity against penicillin-susceptible
and penicillin-resistant pneumococci, covers the atypical bacteria and
is useful for H. influenza and Neisseria gonorrhea.
* Many other quinolones are being de
veloped and promoted. The advantages of the new generation
quinolones are once a day dosing and a wider spectrum of antibacterial
activity.



METRONIDAZOLE:



* Metronidazole
(Flagyl) is indicated mainly for anaerobic coverage. It has
good activity against C. difficile (given PO), Trichomonas, Giardia
and B. fragilis. It may cause a disulfiram-like effect when consumed
with ETOH.



CLINDAMYCIN:



* Clindamycin is excellent against anaerobes, including such below
the diaphragm pathogens as B. fragilis. It also covers streptococci
and S. aureus (not MRSA). It is well absorbed orally. It is the most
frequent cause of C. difficile pseudomembranous colitis.



TMP/SMX:



* (Bactrim) has wide spectrum including activity against
streptococci and H. influenza.

* Indicated PO for uncomplicated UTI, COPD/bronchitis, otitis
media and PCP prophylaxis.

* It is indicated IV for active PCP with pO2 < 70 mmHg or if
unable to tolerate PO. It is given as TMP/SMX (TMP 20mg/kg/day
divided into 4 doses). In HIV (+) pt allergic effects are as high as
50%. Drug should also be avoided in G6PD deficiency.

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