904 SECTION VIII Chemotherapeutic Drugs

TABLE 51–1 Empiric antimicrobial therapy based on microbiologic etiology.

Suspected or Proven Disease or Pathogen Drugs of First Choice
Gram-negative cocci (aerobic)
1 3
Moraxella (Branhamella) catarrhalis TMP-SMZ, cephalosporin
2
(second- or third-generation)
Neisseria gonorrhoeae Ceftriaxone, cefixime
Neisseria meningitides Penicillin G
Gram-negative rods (aerobic)
E coli, Klebsiella, Proteus Cephalosporin (first- or second-
2 1
generation), TMP-SMZ
1 3
Enterobacter, Citrobacter, Serratia TMP-SMZ, quinolone,
6
carbapenem
3 1
Shigella Quinolone
3
Salmonella Quinolone, ceftriaxone
Campylobacter jejuni Erythromycin or azithromycin
Brucella species Doxycycline + rifampin or
aminoglycoside5
Helicobacter pylori Proton pump inhibitor + amoxi-
cillin + clarithromycin
Vibrio species Tetracycline
Pseudomonas aeruginosa Antipseudomonal penicillin ±
aminoglycoside5
Burkholderia cepacia (formerly Pseudomonas TMP-SMZ1
cepacia)
Stenotrophomonas maltophilia (formerly TMP-SMZ1
Xanthomonas maltophilia)
Legionella species Azithromycin or quinolone3
Gram-positive cocci (aerobic)
Streptococcus pneumoniae Penicillin8
Streptococcus pyogenes (group A) Penicillin, clindamycin
5
Streptococcus agalactiae (group B) Penicillin (± aminoglycoside )
Viridans streptococci Penicillin
Staphylococcus aureus
β-Lactamase negative Penicillin
9
β-Lactamase positive Penicillinase-resistant penicillin
Methicillin-resistant Vancomycin
10 5 5
Enterococcus species Penicillin ± aminoglycoside
Gram-positive rods (aerobic)
Bacillus species (non-anthracis) Vancomycin
Listeria species Ampicillin (± aminoglycoside5)
1
Nocardia species Sulfadiazine, TMP-SMZ
Anaerobic bacteria
Gram-positive (clostridia, Peptococcus, Penicillin, clindamycin
Actinomyces, Peptostreptococcus)
Clostridium difficile Metronidazole
Bacteroides fragilis Metronidazole
Alternative Drugs
4
Quinolone, macrolide
Spectinomycin, azithromycin
Chloramphenicol, ceftriaxone, cefotaxime
Quinolone,3 aminoglycoside5
7 5
Antipseudomonal penicillin, aminoglycoside, cefepime
TMP-SMZ, ampicillin, azithromycin, ceftriaxone
Chloramphenicol, ampicillin, TMP-SMZ1
Tetracycline, quinolone3
Chloramphenicol + aminoglycoside5 or TMP-SMZ1
Bismuth + metronidazole + tetracycline + proton pump
inhibitor
Quinolone,3 TMP-SMZ1
3
Antipseudomonal penicillin ± quinolone, cefepime,
6
ceftazidime, antipseudomonal carbapenem, or aztreonam
5
± aminoglycoside
Ceftazidime, chloramphenicol
Minocycline, ticarcillin-clavulanate, tigecycline,
3
ceftazidime, quinolone
Clarithromycin, erythromycin
Doxycycline, ceftriaxone, antipneumococcal quinolone,3
macrolide,4 linezolid
2
Erythromycin, cephalosporin (first-generation)
Vancomycin
2
Cephalosporin (first- or third-generation), vancomycin
Cephalosporin (first-generation),2 vancomycin
As above
TMP-SMZ,1 minocycline, linezolid, daptomycin, tigecycline
Vancomycin ± aminoglycoside
3
Imipenem, quinolone, clindamycin
1
TMP-SMZ
Minocycline, imipenem, amikacin, linezolid
6
Vancomycin, carbapenem, chloramphenicol
Vancomycin, bacitracin
Chloramphenicol, carbapenem,6 β-lactam–β-lactamase-
inhibitor combinations, clindamycin
(continued )
 CHAPTER 51 Clinical Use of Antimicrobial Agents 905

TABLE 51–1 Empiric antimicrobial therapy based on microbiologic etiology. (Continued)

Suspected or Proven Disease or Pathogen Drugs of First Choice Alternative Drugs

Fusobacterium, Prevotella, Porphyromonas Metronidazole, clindamycin, As for B fragilis

penicillin
Mycobacteria
Mycobacterium tuberculosis Isoniazid + rifampin + Streptomycin, moxifloxacin, amikacin, ethionamide,
ethambutol + pyrazinamide cycloserine, PAS, linezolid
Mycobacterium leprae
Multibacillary Dapsone + rifampin +
clofazimine
Paucibacillary Dapsone + rifampin
Mycoplasma pneumoniae Tetracycline, erythromycin Azithromycin, clarithromycin, quinolone3
Chlamydia
C trachomatis Tetracycline, azithromycin Clindamycin, ofloxacin
C pneumoniae Tetracycline, erythromycin Clarithromycin, azithromycin
C psittaci Tetracycline Chloramphenicol
Spirochetes
Borrelia recurrentis Doxycycline Erythromycin, chloramphenicol, penicillin
Borrelia burgdorferi
Early Doxycycline, amoxicillin Cefuroxime axetil, penicillin
Late Ceftriaxone
Leptospira species Penicillin Tetracycline
Treponema species Penicillin Tetracycline, azithromycin, ceftriaxone
Fungi
Aspergillus species Voriconazole Amphotericin B, itraconazole, caspofungin
Blastomyces species Amphotericin B Itraconazole, fluconazole
11
Candida species Amphotericin B, echinocandin Fluconazole, itraconazole, voriconazole
Cryptococcus Amphotericin B ± flucytosine Fluconazole, voriconazole
(5-FC)
Coccidioides immitis Amphotericin B Fluconazole, itraconazole, voriconazole, posaconazole
Histoplasma capsulatum Amphotericin B Itraconazole
Mucoraceae (Rhizopus, Absidia) Amphotericin B Posaconazole
Sporothrix schenckii Amphotericin B Itraconazole
1
Trimethoprim-sulfamethoxazole (TMP-SMZ) is a mixture of one part trimethoprim plus five parts sulfamethoxazole.
2
First-generation cephalosporins: cefazolin for parenteral administration; cefadroxil or cephalexin for oral administration. Second-generation cephalosporins: cefuroxime for
parenteral administration; cefaclor, cefuroxime axetil, cefprozil for oral administration. Third-generation cephalosporins: ceftazidime, cefotaxime, ceftriaxone for parenteral
administration; cefixime, cefpodoxime, ceftibuten, cefdinir, cefditoren for oral administration. Fourth-generation cephalosporin: cefepime for parenteral administration.
Cephamycins: cefoxitin and cefotetan for parenteral administration.
3
Quinolones: ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin. Norfloxacin is not effective for the treatment of systemic infections. Gemifloxacin,
levofloxacin, and moxifloxacin have excellent activity against pneumococci. Ciprofloxacin and levofloxacin have good activity against Pseudomonas aeruginosa.
4
Macrolides: azithromycin, clarithromycin, dirithromycin, erythromycin.
5
Generally, streptomycin and gentamicin are used to treat infections with gram-positive organisms, whereas gentamicin, tobramycin, and amikacin are used to treat infections
with gram-negatives.
6
Carbapenems: doripenem, ertapenem, imipenem, meropenem. Ertapenem lacks activity against enterococci, Acinetobacter, and P aeruginosa.
7
Antipseudomonal penicillin: piperacillin, piperacillin/tazobactam, ticarcillin/clavulanic acid.
8
See footnote 3 in Table 51–2 for guidelines on the treatment of penicillin-resistant pneumococcal meningitis.
9
Parenteral nafcillin or oxacillin; oral dicloxacillin.
10
There is no regimen that is reliably bactericidal for vancomycin-resistant enterococcus for which there is extensive clinical experience; daptomycin has bactericidal activity in
vitro. Regimens that have been reported to be efficacious include nitrofurantoin (for urinary tract infection); potential regimens for bacteremia include daptomycin, linezolid,
and dalfopristin/quinupristin.
11
Echinocandins: anidulafungin, caspofungin, micafungin.
906 SECTION VIII Chemotherapeutic Drugs

TABLE 51–2 Empiric antimicrobial therapy based on site of infection.

Presumed Site of Infection Common Pathogens Drugs of First Choice Alternative Drugs

Bacterial endocarditis
Acute Staphylococcus aureus Vancomycin + gentamicin Penicillinase-resistant
1
penicillin + gentamicin
Subacute Viridans streptococci, enterococci Penicillin + gentamicin Vancomycin + gentamicin
Septic arthritis
Child H influenzae, S aureus, β-hemolytic Ceftriaxone Ampicillin-sulbactam
streptococci
Adult S aureus, Enterobacteriaceae Cefazolin Vancomycin, quinolone
Acute otitis media, H influenzae, S pneumoniae, Amoxicillin Amoxicillin-clavulanate,
sinusitis M catarrhalis cefuroxime axetil, TMP-SMZ
Cellulitis S aureus, group A streptococcus Penicillinase-resistant penicillin, Vancomycin, clindamycin,
cephalosporin (first-generation)2 linezolid, daptomycin
Meningitis
Neonate Group B streptococcus, E coli, Listeria Ampicillin + cephalosporin (third- Ampicillin + aminoglycoside,
generation) chloramphenicol, meropenem
Child H influenzae, pneumococcus, Ceftriaxone or cefotaxime ± Chloramphenicol, meropenem
meningococcus vancomycin3
Adult Pneumococcus, meningococcus Ceftriaxone, cefotaxime Vancomycin + ceftriaxone or
cefotaxime3
Peritonitis due to Coliforms, B fragilis Metronidazole + cephalosporin Carbapenem, tigecycline
ruptured viscus (third-generation), piperacillin/
tazobactam
Pneumonia
Neonate As in neonatal meningitis
Child Pneumococcus, S aureus, H influenzae Ceftriaxone, cefuroxime, cefotaxime Ampicillin-sulbactam
Adult (community- Pneumococcus, Mycoplasma, Outpatient: Macrolide,4 amoxicillin, Outpatient: Quinolone
acquired) Legionella, H influenzae, S aureus, tetracycline
C pneumonia, coliforms
Inpatient: Macrolide4 + cefotaxime, Inpatient: Doxycycline +
ceftriaxone, ertapenem, or ampicillin cefotaxime, ceftriaxone,
ertapenem, or ampicillin;
5
respiratory quinolone
Septicemia6 Any Vancomycin + cephalosporin (third-generation) or piperacillin/
tazobactam or imipenem or meropenem
Septicemia with Any Antipseudomonal penicillin + aminoglycoside; ceftazidime; cefepime;
granulocytopenia imipenem or meropenem; consider addition of systemic antifungal therapy
if fever persists beyond 5 days of empiric therapy
1
See footnote 9, Table 51–1.
2
See footnote 2, Table 51–1.
3
When meningitis with penicillin-resistant pneumococcus is suspected, empiric therapy with this regimen is recommended.
4
Erythromycin, clarithromycin, or azithromycin (an azalide) may be used.
5
Quinolones used to treat pneumonococcal infections include levofloxacin, moxifloxacin, and gemifloxacin.
6
Adjunctive immunomodulatory drugs such as drotrecogin-alfa can also be considered for patients with severe sepsis.

done to maximize it. For example, are adequate numbers of
granulocytes present and are HIV infection, malnutrition, or
underlying malignancy present? The presence of abscesses or for-
eign bodies should also be considered. Finally, culture and suscep-
tibility testing should be repeated to determine whether
superinfection has occurred with another organism or whether the
original pathogen has developed drug resistance.
ANTIMICROBIAL PHARMACODYNAMICS
The time course of drug concentration is closely related to the anti-
microbial effect at the site of infection and to any toxic effects.
Pharmacodynamic factors include pathogen susceptibility testing,
drug bactericidal versus bacteriostatic activity, drug synergism, antag-
onism, and postantibiotic effects. Together with pharmacokinetics,