Choosing Antimicrobials in
Special Situations
Additional considerations in
making a final antibiotic selection
• Site of action
– (Will the antibiotic penetrate into the site of infection and
be active there?)
• Cidal vs. Static activity
– (When is a cidal antimicrobial required?)
• Sodium load
– (Will the sodium content of the antibiotic contribute to fluid
overload and circulatory impairment?)
• Ease of administration
– (Can the number of IVs be minimized for home therapy? Or
can oral drugs be substituted?)
• Microbial ecology of the institution and the
community
– (Will the use of certain agents contribute to resistance in
the larger community?)
Other important considerations
(not discussed in this presentation)
• Covering the spectrum with the minimal
number of drugs”
– See “Principles of Antimicrobial Therapy
• Allergies
– See “Antibiotic Allergies & Adverse Effects”
• Renal dysfunction
– See “Adjustments for Renal & Hepatic Failure”
• Hepatic dysfunction
– See “Adjustments for Renal & Hepatic Failure”
Site of Action: CNS penetration
• Reliable
– high-dose 3rd generation cephalosporins
– high-dose penicillins
– trimethoprim-sulfa
– metronidazole
– chloramphenicol
– quinolones
• Variable: vancomycin, (linezolid)
• Poor
– aminoglycosides
– macrolides and clindamycin
– tetracyclines
– early generation cephalosporins
– daptomycin
Other site-of-action issues
• Abscesses
– Aminoglycosides are inactive at the low pH found in
abscesses
• Lungs
– Daptomycin is ineffective in pneumonia because the
drug partitions in the surfactant layer instead of the
bacterial membrane
• Prostate
– Beta-lactams penetrate poorly. Fluoroquinolones
penetrate reasonably well.
• Urine
– Drugs excreted primarily by the liver do not achieve high
concentrations in high (e.g., ceftriaxone, nafcillin,
clindamycin)
Generalities about microbial
killing
•
Usually cidal drugs
– beta-lactams (except enterococci)
– vancomycin (except enterococci)
– quinolones
– aminoglycosides
– daptomycin
– amphotericin B
•
Usually static drugs
– tetracyclines (e.g., doxy)
– macrolides and clindamycin (for many)
– chloramphenicol (except for meningococci
– imidazoles and triazoles
– linezolid
and pneumococci
When are cidal drugs
essential?
• Meningitis*
• Endocarditis*
• Neutropenic fever*
• (Whenever possible in a serious
infection)
*conditions in which the host is unable to clear the
pathogen even if it is inhibited from growing
Sodium content of commonly used antimicrobials
(from the Cleveland Clinic web site)
Drug Name and Dosage Unit
Acyclovir, 1g
Amikacin sulfate, 1g
Aminosalicylate sodium, 1g
Ampicillin, 1g
Cefazolin sodium, 1g
Ceftazidime, 1g
Ceftizoxime sodium, 1g
Ceftriaxone sodium, 1g
Cefuroxime, 1g
Chloramphenicol, 1g
Colistimethate sodium, 150 mg
Dicloxacillin, 250 mg (capsule)
Dicloxacillin, suspension 65mg/5mL
Didanosine, buffered tablets
Erythromycin ethylsuccinate, susp. 200 mg/5mL
Ganciclovir, 500 mg vial
Imipenem/cilastatin, injection 1 g IV
Imipenem/cilastatin, injection 1 g IM
Metronidazole, 500 mg IV
Oxacillin sodium, 1 g
Penicillin G potassium, 1 million units parenteral
Penicillin G sodium, 1 million units parenteral
Piperacillin/tazobactam, 1 g
Sodium (mg)
96.6
29.9
108.9
66.7
47
54
59.8
59.8
55.2
51.8
22.9
13
27
264.5
29
46
73.6
84.4
322
64.4-71.3
7
46
54
Sodium (mEq)
4.2
1.3
4.7
3
2
2.3
2.6
2.6
2.4
2.25
1
0.6
1.2
11.5
1.3
2
3.2
2.8
14
2.8-3.1
0.3
2
2.35
Ease of Administration
• Once Daily IV Dosing
– Ceftriaxone
– Ertapenem
– Aminoglycosides
– Daptomycin
– Vancomycin (with mild renal impairment)
• Twice Daily IV Dosing
– Vancomycin (with normal renal function)
– Cefotetan
Antibiotics with excellent oral
bioavailability
(may be substituted for IV equivalents)
• Linezolid
• Metronidazole
• Fluconazole
• Fluoroquinolones
• Trimethoprim-sulfamethoxasole