for men, (x0.85 for women)
- 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)
- Note: Some abx do not need adjustement for patients with renal insufficiency (e.g., amphotericin B, azithromycin, ceftriaxone, chloramphenicol, clindamycin, doxycycline, nafcillin, pyrimethamine, rifambutin).
- 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.
- 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.
- Antipseudomonal penicillins:
(carbenicillin and ticarcillin) and ureidoPCN (mezlocillin =Mezlin® and piperacillin = Pipracil®) cover most streptococci, and most G(-) with variable coverage for Klebsiella,
M. catarrhalis, Serratia, Legionella. No coverage for Staphylococcus (except Timentin® and Zosyn®). Good anaerobic coverage (B. fragilis, C. difficile
). Main indication is Pseudomonas aeuroginosa.
- Ticarcillin + clavulanate = Timentin®. Covers G(+) similar to Augmentin® and all G(-) except Legionella. Anaerobic coverage like group III (B. fragilis, C. difficile).
- Piperacillin + tazobactam = Zosyn®. Similar to Timentin®. Note that for serious Pseudomonas infections an aminoglycoside should be added for synergism.
- 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.
(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)
- 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.
(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.
- 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
- 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.
- 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.
- 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.
- 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.
- Until the 1990's, erythromycin was the primary representative of the macrolide class of antibiotics. In 1991, clarithromycin (Biaxin) and azithromycin (Zithromax®) 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®)
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.
- 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
- 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.
(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 (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 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.
- (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.