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Overview of Antibacterial Drugs

by Hans P. Schlecht, MD, MSc, Christopher Bruno, MD

Antibacterial drugs are derived from bacteria or molds or are synthesized de novo. Technically, “antibiotic” refers only to antimicrobials derived from bacteria or molds but is often (including in The Manual ) used synonymously with “antibacterial drug.”

Antibiotics have many mechanisms of action, including inhibiting cell wall synthesis, l, increasing cell membrane permeability, and interfering with protein synthesis, nucleic acid metabolism, and other metabolic processes (eg, folic acid synthesis).

Antibiotics sometimes interact with other drugs, raising or lowering serum levels of other drugs by increasing or decreasing their metabolism or by various other mechanisms (see Table: Common Effects of Antibiotics on Other Drugs). The most clinically important interactions involve drugs with a low therapeutic ratio (ie, toxic levels are close to therapeutic levels). Also, other drugs can increase or decrease levels of antibiotics.

Many antibiotics are chemically related and are thus grouped into classes. Although drugs within each class share structural and functional similarities, they often have different pharmacology and spectra of activity.

Common Effects of Antibiotics on Other Drugs

Drug

Toxicity Enhanced By

No Change With

Digoxin

All macrolides (eg, azithromycin, clarithromycin, erythromycin)

Doxycycline

Tetracycline

Trimethoprim

Aminoglycosides

Cephalosporins

Clindamycin

Fluoroquinolones

Ketoconazole

Linezolid

Metronidazole

Penicillins

Quinulpristine/dalfopristin

Sulfonamides

Vancomycin

Phenytoin

Chloramphenicol

Ciprofloxacin

Isoniazid

Some macrolides (erythromycin, clarithromycin, telithromycin)

Rifampin (decreased phenytoin levels)

Sulfonamides

Azithromycin

Aminoglycosides

Cephalosporins

Clindamycin

Doxycycline

Fluoroquinolones except ciprofloxacin

Linezolid

Metronidazole

Penicillins

Quinulpristine/dalfopristin

Tetracycline

Trimethoprim

Vancomycin

Theophylline

Ciprofloxacin

Clarithromycin

Erythromycin

Rifampin (decreased theophylline levels)

Aminoglycosides

Azithromycin

Cephalosporins

Clindamycin

Doxycycline

Linezolid

Metronidazole

Penicillins

Quinulpristine/dalfopristin

Sulfonamides

Tetracycline

Trimethoprim

Vancomycin

Warfarin*

Cefoperazone

Cefotetan

Chloramphenicol

Clarithromycin

Doxycycline

Erythromycin

Certain fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin)

Metronidazole

Rifampin (decreased PT)

Sulfonamides

Aminoglycosides (IV)

Azithromycin

Cephalosporins (some)

Clindamycin

Doxycycline

Linezolid

Penicillins

Quinulpristine/dalfopristin

Tetracycline

Trimethoprim

Vancomycin

.

These drugs interfere with vitamin K–dependent clotting factors and, when used with antiplatelet drugs and thrombolytics, may increase risk of bleeding.

Selection and Use of Antibiotics

Antibiotics should be used only if clinical or laboratory evidence suggests bacterial infection. Use for viral illness or undifferentiated fever is inappropriate in most cases; it exposes patients to drug complications without any benefit and contributes to bacterial resistance.

Certain bacterial infections (eg, abscesses, infections with foreign bodies) require surgical intervention and do not respond to antibiotics alone.

Spectrum of activity

Cultures and antibiotic sensitivity testing are essential for selecting a drug for serious infections. However, treatment must often begin before culture results are available, necessitating selection according to the most likely pathogens (empiric antibiotic selection).

Whether chosen according to culture results or not, drugs with the narrowest spectrum of activity that can control the infection should be used. For empiric treatment of serious infections that may involve any one of several pathogens (eg, fever in neutropenic patients) or that may be due to multiple pathogens (eg, polymicrobial anaerobic infection), a broad spectrum of activity is desirable. The most likely pathogens and their susceptibility to antibiotics vary according to geographic location (within cities or even within a hospital) and can change from month to month.

For serious infections, combinations of antibiotics are often necessary because multiple species of bacteria may be present or because combinations act synergistically against a single species of bacteria. Synergism is usually defined as a more rapid and complete bactericidal action from a combination of antibiotics than occurs with either antibiotic alone. A common example is a cell wall–active antibiotic (eg, a β-lactam, vancomycin) plus an aminoglycoside.


Effectiveness

In vivo antibiotic effectiveness involves many factors, including

  • Pharmacology (eg, absorption, distribution, concentration in fluids and tissues, protein binding, rate of metabolism or excretion)

  • Pharmacodynamics (ie, the time course of antibacterial effects exerted by drug levels in blood and at the site of infection)

  • Drug interactions or inhibiting substances

  • Host defense mechanisms

Bactericidal drugs kill bacteria. Bacteriostatic drugs slow or stop in vitro bacterial growth. These definitions are not absolute; bacteriostatic drugs may kill some susceptible bacterial species, and bactericidal drugs may only inhibit growth of some susceptible bacterial species. Bactericidal antibiotics may be preferred for patients who have infections that impair host defenses locally (eg, meningitis, endocarditis) or who are immunocompromised (eg, neutropenic). More precise quantitative methods identify the minimum in vitro concentration at which an antibiotic can inhibit growth (minimum inhibitory concentration, or MIC) or kill (minimum bactericidal concentration, or MBC). An antibiotic with bactericidal activity is important if host defenses are impaired locally at the site of infection (eg, in meningitis or endocarditis) or systemically (eg, in patients who are neutropenic or immunocompromised in other ways).

The predominant determinant of bacteriologic response to antibiotics is either the

  • Time that blood levels of the antibiotic exceed the MIC (time-dependence)

  • Peak blood level relative to MIC (concentration-dependence)

β -Lactams and vancomycin exhibit time-dependent bactericidal activity. Increasing their concentration above the MIC does not increase their bactericidal activity, and their in vivo killing is generally slow. In addition, because there is no or very brief residual inhibition of bacterial growth after concentrations fall below the MIC (postantibiotic effect, or PAE), β-lactams are most often effective when serum levels of free drug (drug not bound to serum protein) exceed the MIC for 50% of the time. Because ceftriaxone has a long serum half-life, free serum levels exceed the MIC of very susceptible pathogens for the entire 24-h dosing interval. However, for β-lactams that have serum half-lives of 2 h, frequent dosing or continuous infusion is required. For vancomycin, trough levels should be maintained at least at 15 to 20 μg/mL.

Aminoglycosides, fluoroquinolones, and daptomycin exhibit concentration-dependent bactericidal activity. Increasing their concentrations from levels slightly above the MIC to levels far above the MIC increases their rate of bactericidal activity and decreases the bacterial load. In addition, if concentrations exceed the MIC even briefly, aminoglycosides and fluoroquinolones have a PAE on residual bacteria; duration of PAE is also concentration-dependent. If PAEs are long, drug levels can be below the MIC for extended periods without loss of efficacy, allowing less frequent dosing. Consequently, aminoglycosides and fluoroquinolones are usually most effective as intermittent boluses that reach peak free serum levels 10 times the MIC of the bacteria; usually, trough levels are not important.


Route

For many antibiotics, oral administration results in therapeutic blood levels nearly as rapidly as IV administration. However, IV administration is preferred in the following circumstances:

  • Oral antibiotics cannot be tolerated (eg, because of vomiting).

  • Oral antibiotics cannot be absorbed (eg, because of malabsorption after intestinal surgery).

  • Intestinal motility is impaired (eg, because of opioid use).

  • No oral formulation is available (eg, for aminoglycosides).

  • Patients are critically ill, possibly impairing GI tract perfusion or making even the brief delay with oral administration detrimental.


Special populations

Doses and scheduling of antibiotics may need to be adjusted for the following:

  • Infants

  • The elderly

  • Patients with renal failure (see Table: Usual Doses of Commonly Prescribed Antibiotics)

  • Patients with hepatic insufficiency (most commonly for cefoperazone, chloramphenicol, metronidazole, rifabutin, and rifampin)

Pregnancy and breastfeeding affect choice of antibiotic. Penicillins, cephalosporins, and erythromycin are among the safest antibiotics during pregnancy; tetracyclines are contraindicated. Most antibiotics reach sufficient concentrations in breast milk to affect a breastfed baby, sometimes contraindicating their use in women who are breastfeeding.

Usual Doses of Commonly Prescribed Antibiotics

Drug

Adult Dose

Pediatric (Age > 1 mo) Dose

Dose in Renal Failure a (CrCl < 10 mL/min)

Oral

Parenteral

Serious Infections

Oral

Parenteral

Aminoglycosides

Amikacin

N/A

15 mg/kg IV once/day

or

7.5 mg/kg q 12 h

15 mg/kg IV once/day

or

7.5 mg/kg IV q 12 h

N/A

5–7.5 mg/kg IV q 12 h

1.5–2.5 mg/kg IV q 24–48 h

Gentamicin

N/A

5–7 mg/kg IV once/day

or

1.7 mg/kg IV q 8 h

5–7 mg/kg IV once/day

N/A

1–2.5 mg/kg IV q 8 h

0.34–0.51 mg/kg IV q 24–48 h

For synergy with a cell wall–active antibiotic to treat enterococcal endocarditis caused by strains susceptible to gentamicin

N/A

1 mg/kg IV q 8 h

N/A

N/A

1 mg/kg IV q 8 h

Infectious disease consultation required for dosage

Dosage adjusted to achieve peak serum concentration of 3–4 μg/mL and trough concentration of < 1 μg/mL

For streptococcal or Staphylococcus aureus endocarditis

1 mg/kg IV q 8 h

or

3 mg/kg IV once/day

N/A

N/A

1 mg/kg IV q 8 h

or

3 mg/kg IV once/day

N/A

Neomycin

For preoperative gut antisepsis (with erythromycin and mechanical cleansing)

1 g for 3 doses (eg, at 1, 2, and 11 pm on the day before surgery)

N/A

N/A

15 mg/kg q 4 h for 2 days

or

25 mg/kg at 1, 2, and 11 pm on the day before surgery

N/A

N/A

For hepatic coma

1–3 g qid

N/A

N/A

0.6–1.75 g/m 2 q 6 h

or

0.4–1.2 g/m 2 q 4 h

N/A

N/A

Streptomycin

For TB

N/A

15 mg/kg IM q 24 h (maximum: 1.0 g/day) initially, then 1.0 g 2–3 times/wk

N/A

N/A

20–40 mg/kg IM once/day

7.5 mg/kg IM q 72–96 h (maximum: 1 g)

For synergy with a cell wall–active antibiotic to treat enterococcal endocarditis

N/A

7.5 mg/kg IM q 12 h

N/A

N/A

N/A

N/A

Tobramycin

N/A

5–7 mg/kg IV once/day

or

1.7 mg/kg IV q 8 h

5–7 mg/kg IV once/day

or

1.7 mg/kg IV q 8 h

N/A

1–2.5 mg/kg IV q 8 h

0.34–0.51 mg/kg IV q 24–48 h

β-Lactams: Cephalosporins (1st generation)

Cefadroxil

0.5–1 g q 12 h

N/A

N/A

15 mg/kg q 12 h

N/A

0.5 g po q 36 h

Cefazolin

N/A

1–2 g IV q 8 h

2 g IV q 8 h

N/A

16.6–33.3 mg/kg IV q 8 h

1–2 g IV q 24–48 h

Cephalexin

0.25–0.5 g q 6 h

N/A

N/A

6.25–12.5 mg/kg q 6 h

or

8.0–16 mg/kg q 8 h

N/A

0.25–0.5 g po q 24–48 h

β-Lactams: Cephalosporins (2nd generation)

Cefaclor b

0.25–0.5 g q 8 h

N/A

N/A

10–20 mg/kg q 12 h

or

6.6–13.3 mg/kg q 8 h

N/A

0.5 g po q 12 h

Cefotetan

N/A

1–3 g IV q 12 h

2–3 g IV q 12 h

N/A

20–40 mg/kg IV q 12 h

1–3 g IV q 48 h

Cefoxitin

N/A

1 g IV q 8 h to 2 g IV q 4 h

2 g IV q 4 h

or

3 g IV q 6 h

N/A

27–33 mg/kg IV q 8 h or, for severe infections, 25–40 mg/kg q 6 h

0.5–1.0 g IV q 24–48 h

Cefprozil

0.25 g q 12 h

or

0.5 g q 12–24 h

N/A

N/A

15 mg/kg q 12 h for otitis media

N/A

0.25 g po q 12–24 h

Cefuroxime

0.125–0.5 g q 12 h

0.75–1.5 g IV q 6–8 h

1.5 g IV q 6 h

10–15 mg/kg suspension q 12 h

For older children: 125–250 mg tablets q 12 h

25–50 mg/kg IV q 8 h

0.25–0.5 g po q 24 h

or

0.75 g IV q 24 h

For meningitis

3 g IV q 8 h

50–60 mg/kg IV q 6 h

β-Lactams: Cephalosporins (3rd generation)

Cefotaxime

N/A

1 g q 12 h to 2 g IV q 4 h

2 g IV q 4 h

N/A

8.3–33.3 mg/kg IV q 4 h

or

16.6–66.6 mg/kg q 6 h

1–2 g IV q 24 h

Cefpodoxime c

0.1–0.4 g q 12 h

N/A

N/A

5 mg/kg q 12 h

N/A

0.1–0.4 g po q 24 h

Ceftazidime

N/A

1 g IV q 12 h to 2 g q 8 h

2 g IV q 8 h

N/A

25–50 mg/kg IV q 8 h

0.5 g IV q 24–48 h

Ceftibuten b

0.4 g q 24 h

N/A

N/A

9 mg/kg once/day

N/A

0.1 g po q 24 h

Ceftriaxone

N/A

1–2 g IV q 24 h

2 g IV q 24 h

N/A

50–75 mg/kg IV q 24 h

or

25–37.5 mg/kg q 12 h

Same as adult dose

For meningitis

N/A

2 g IV q 12 h

2 g IV q 12 h

N/A

50 mg/kg IV q 12 h or 100 mg/kg q 24 h (not to exceed 4 g/day)

Possibly a loading dose of 100 mg/kg IV (not to exceed 4 g) at the start of therapy

2 g IV q 12 h

β-Lactams: Cephalosporin (4th generation)

Cefepime

N/A

1–2 g IV q 8–12 h

2 g IV q 8 h

N/A

50 mg/kg IV q 8–12 h

0.25–1 g IV q 24 h

β-Lactams: Cephalosporin (5th generation)

Ceftaroline

N/A

0.6 g IV q 12 h

0.6 g IV q 12 h

N/A

N/A

0.2 g IV q 12 h

β-Lactams: Penicillins

Amoxicillin

0.25–0.5 g q 8 h

or

0.875 g q 12 h

N/A

N/A

12.5–25 mg/kg q 12 h

or

7–13 mg/kg q 8 h

N/A

0.25–0.5 g po q 24 h

For endocarditis prophylaxis

2 g for 1 dose

N/A

N/A

50 mg/kg 1 h before procedure

N/A

2 g po for 1 dose

Amoxicillin/clavulanate

0.25–0.5 g q 8 h

or

0.875 g q 12 h

N/A

N/A

If > 40 kg: Adult dose

N/A

0.25–0.5 g po q 24 h

Amoxicillin/clavulanate, ES-600

N/A

N/A

N/A

45 mg/kg q 12 h

N/A

N/A

Amoxicillin/clavulanate, extended-release

2 g q 12 h

N/A

N/A

N/A

N/A

N/A

Ampicillin

N/A

0.5–2.0 g IV q 4–6 h

2 g IV q 4 h

N/A

25–50 mg/kg IV q 6 h

0.5–2.0 g IV q 12–24 h

For meningitis

N/A

2 g IV q 4 h

2 g IV q 4 h

N/A

50–100 mg/kg IV q 6 h

2 g IV q 12 h

Ampicillin/sulbactam

(3 g = 2 g ampicillin + 1 g sulbactam)

N/A

1.5–3.0 g IV q 6 h

3 g IV q 6 h

N/A

25–50 mg/kg IV q 6 h

1.5–3.0 g IV q 24 h

Dicloxacillin b

0.125–0.5 g q 6 h

N/A

N/A

3.125–6.25 mg/kg q 6 h

N/A

0.125–0.5 g po q 6 h

Nafcillin

Rarely used

1–2 g IV q 4 h

2 g IV q 4 h

N/A

12.5–25 mg/kg IV q 6 h

or

8.3–33.3 mg/kg q 4 h

1–2 g IV q 4 h

Oxacillin

Rarely used

1–2 g IV q 4 h

2 g IV q 4 h

N/A

12.5–25 mg/kg IV q 6 h

or

8.3–33.3 mg/kg IV q 4 h

1–2 g IV q 4 h

Penicillin G b

0.25–0.5 g q 6–12 h (penicillin V)

1–4 million units IV q 4–6 h

4 million units IV q 4 h

Penicillin VK

6.25–12.5 mg/kg q 8 h

6,250–100,000 units/kg IV q 6 h

or

4,166.6–66,666 units/kg IV q 4 h

0.5–2 million units IV q 4–6 h (maximum total daily dose: 6 million units/day)

Penicillin G benzathine (Bicillin© L-A)

For streptococcal pharyngitis

N/A

1.2 million units IM for 1 dose

N/A

N/A

25,000–50,000 units/kg IM as a single dose

or

If < 27 kg: 300,000–600,000 units as a single dose

or

If 27 kg: 0.9 million units as a single dose

1.2 million units IM for 1 dose

Prophylaxis for rheumatic fever

N/A

1.2 million units IM q 3–4 wk

N/A

N/A

25,000–50,000 units/kg IM q 3–4 wk

1.2 million units IM q 3–4 wk

For early syphilis

N/A

2.4 million units IM for 1 dose

N/A

N/A

50,000 units/kg IM for 1 dose

2.4 million units IM for 1 dose

For late syphilis (excluding neurosyphilis)

N/A

2.4 million units IM/wk for 3 wk

N/A

N/A

50,000 units/kg IM in 3 doses 1 wk apart

2.4 million units IM for 1 dose

Penicillin G procaine (IM only)

N/A

0.3–0.6 million units IM q 12 h

N/A

N/A

25,000–50,000 units/kg IM q 24 h

or

12,500–25,000 units/kg IM q 12 h

0.3 to 0.6 million units IM q 12 h

Piperacillin (1.9 mEq Na/g)

N/A

3 g IV q 4–6 h

3 g IV q 4 h

N/A

50–75 mg/kg IV q 6 h

or

33.3–50 mg/kg IV q 4 h

3–4 g IV q 12 h

Piperacillin/tazobactam (2.25 g = 2.0 g piperacillin + 0.25 g tazobactam)

N/A

3.375 g IV q 4–6 h

3.375 g IV q 4 h

N/A

80 mg/kg IV q 8 h

2.25 g IV q 8 h to 4.5 g IV q 12 h

Ticarcillin (5.2 mEq Na/g)

N/A

3 g IV q 4–6 h

3 g IV q 4 h

N/A

If < 60 kg: 50 mg/kg IV q 4–6 h

1–2 g IV q 12 h

Ticarcillin/clavulanate (3.1 g = 3 g ticarcillin + 0.1 g clavulanic acid)

N/A

3.1 g IV q 4–6 h

3.1 g IV q 4 h

N/A

If < 60 kg: 50 mg/kg IV (based on ticarcillin component) q 4–6 h

2 g IV q 12 h

β-Lactams: Monobactams

Aztreonam

N/A

1–2 g IV q 6–12 h

2 g IV q 6 h

N/A

30–40 mg/kg IV q 6–8 h

0.5 g IV q 8 h

β-Lactams: Carbapenems

Ertapenem

N/A

1 g IV q 24 h

1 g IV q 24 h

N/A

N/A

0.5 g IV q 24 h

Imipenem

N/A

0.5–1.0 g IV q 6 h

1 g IV q 6 h

N/A

For infants 4 wk to 3 mo: 25 mg/kg IV q 6 h

For children >3 mo: 15–25 mg/kg IV q 6 h

0.125–0.25 g IV q 12 h (may increase risk of seizures)

Meropenem

N/A

1 g IV q 8 h

2 g IV q 8 h

N/A

20–40 mg/kg IV q 8 h

0.5 g IV q 24 h

Doripenem

N/A

0.5 g IV q 8 h

0.5 g IV q 8 h

N/A

N/A

0.25 g IV q 24 h

For meningitis

40 mg/kg IV q 8 h

40 mg/kg IV q 8 h

N/A

20 mg/kg IV q 24 h

Fluoroquinolones d

Ciprofloxacin

0.5–0.75 g q 12 h

0.2–0.4 g IV q 8–12 h

0.4 g IV q 8 h

10–15 mg/kg IV q 12 h (in select circumstances)

10–15 mg/kg IV q 12 h (in select circumstances)

0.5–0.75 g po q 24 h

or

0.2–0.4 g IV q 24 h

Extended-release for uncomplicated cystitis

0.5 g q 24 h for 3 days

N/A

N/A

N/A

N/A

N/A

Gemifloxacin

320 mg q 24 h

N/A

N/A

N/A

N/A

160 mg po q 24 h

Levofloxacin

0.25–0.75 g q 24 h

0.25–0.75 IV g q 24 h

0.75 g IV q 24 h

N/A

N/A

0.25–0.5 g po or IV q 48 h

Moxifloxacin

0.4 g q 24 h

0.4 g IV q 24 h

0.4 g IV q 24 h

N/A

N/A

0.4 g q 24 h po or IV

Norfloxacin b

0.4 g q 12 h

N/A

N/A

N/A

N/A

0.4 g po q 24 h

Ofloxacin

0.2–0.4 g q 12 h

0.4 g IV q 12 h

0.2–0.4 g IV q 12 h

N/A

N/A

0.1–0.2 g po or IV q 24 h

Macrolides

Azithromycin

0.5 g on day 1, then 0.25 g q 24 h for 4 days

0.5 g IV q 24 h

0.5 g IV q 24 h

N/A

0.5 g po on day 1, then 0.25 g po q 24 h for 4 days or 0.5 g IV q 24 h

For nongonococcal cervicitis and urethritis

1 g for 1 dose

N/A

N/A

N/A

N/A

N/A

For traveler’s diarrhea

1 g for 1dose

N/A

N/A

5–10 mg/kg for 1 dose

N/A

N/A

For tonsillitis or pharyngitis

N/A

N/A

N/A

12 mg/kg for 5 days

N/A

N/A

For otitis media or community-acquired pneumonia

N/A

N/A

N/A

10 mg/kg on day 1, then 5 mg/kg once/day on days 2–5

N/A

N/A

Clarithromycin

0.25–0.5 g q 12 h

Extended-release: 1 g q 24 h

N/A

N/A

7.5 mg/kg q 12 h

N/A

0.25–0.5 g po q 24 h

Erythromycin base b

0.25–0.5 g q 6 h

N/A

N/A

10–16.6 mg/kg q 8 h

or

7.5–12.5 mg/kg q 6 h

N/A

0.25 g po q 6 h

Fidaxomicin

0.2 g q 12 h

N/A

N/A

N/A

N/A

0.2 g po q 12 h

Lactobionate

N/A

0.5–1 g IV q 6 h

1 g IV q 6 h

N/A

3.75–5.0 mg/kg IV q 6 h

0.5 g IV q 6 h

Gluceptate

N/A

0.5–1 g IV q 6 h

1 g IV q 6 h

N/A

3.75–5.0 mg/kg IV q 6 h

0.5 g IV q 6 h

For GI preoperative bowel preparation

1 g for 3 doses

N/A

N/A

20 mg/kg for 3 doses

N/A

N/A

Telithromycin

800 mg q 24 h

N/A

N/A

N/A

N/A

800 mg po q 24 h

Sulfonamides and trimethoprim

Sulfisoxazole

1.0 g q 6 h

25 mg/kg IV q 6 h (not available in US)

N/A

30–37.5 mg/kg q 6 h

or

20–25 mg/kg q 4 h

N/A

1 g po q 12–24 h

Sulfamethizole

0.5–1 g q 6–8 h

N/A

N/A

7.5–11.25 mg/kg q 6 h

N/A

N/A

Sulfamethoxazole

1 g q 8–12 h

N/A

N/A

25–30 mg/kg q 12 h

N/A

1 g po q 24 h

Trimethoprim

0.1 g q 12 h

or

0.2 g q 24 h

N/A

N/A

2 mg/kg q 12 h for 10 days for UTI

N/A

0.1 g po q 24 h

Trimethoprim/sulfamethoxazole e

0.16/0.8 g q 12 h

3–5 mg TMP/kg IV q 6–8 h

5 mg TMP/kg IV q 6 h

3–6 mg TMP/kg q 12 h

3–6 mg TMP/kg IV q 12 h

(Not recommended if other alternatives are available)

For Pneumocystis jiroveciipneumonia e

0.32/1.6 g q 8 h for 21 days

5 mg TMP/kg IV q 8 h for 21 days

5 mg TMP/kg IV q 6–8 h

5–6.6 mg TMP/kg q 8 h

or

3.75–5 mg TMP/kg q 6 h

5–6.6 mg TMP/kg IV q 8 h

or

3.75–5 mg TMP/kg IV q 6 h

If essential, 5 mg TMP/kg IV q 24 h

or

1.25 mg TMP/kg IV q 6 h

Tetracyclines

Doxycycline

0.1 g q 12 h

0.1 g IV q 12 h

0.1 mg IV q 12 h

Age > 8 yr: 2–4 mg/kg q 24 h

or

1–2 mg/kg q 12 h

Age > 8 yr: 2–4 mg/kg IV q 24 h

or

1–2 mg/kg IV q 12 h

0.1 g IV or po q 12 h

Minocycline

0.1 g q 12 h

0.1 g IV q 12 h

0.1 g IV q 12 h

N/A

N/A

0.1 g IV or po q 12 h

Tetracycline b

0.25–0.5 g q 6 h

N/A

N/A

Age > 8 yr: 6.25–12.5 mg/kg q 6 h

N/A

Doxycycline used instead

Tigecycline

N/A

100 mg, then 50 mg (25 mg for severe hepatic dysfunction) IV q 12 hr

Same as adult dose f

N/A

N/A

Same as adult dose

Others

Clindamycin

0.15–0.45 g q 6 h

0.6 g IV q 6 h to 0.9 IV g q 8 h

0.9 g IV q 8 h

2.6–6.6 mg/kg q 8 h

or

2–5 mg/kg q 6 h

6.6–13.2 mg/kg IV q 8 h

or

5–10 mg/kg IV q 6 h

0.15–0.45 g po q 6 h

or

0.6–0.9 g IV q 6–8 h

Chloramphenicol

0.25–1 g q 6 h

0.25–1.0 g IV q 6 h

1 g IV q 6 h

N/A

12.5–18.75 mg/kg IV q 6 h

0.25–1.0 g IV q 6 h

For meningitis

N/A

12.5 mg/kg q 6 h (maximum: 4 g/day)

12.5 mg/kg IV q 6 h (maximum: 4 g/day)

N/A

18.75–25 mg/kg IV q 6 h

12.5 mg/kg IV q 6 h (maximum: 4 g/day)

Colistin (polymyxin E)

N/A

2.5–5 mg/kg/day IV in 2–4 doses

2.5–5 mg/kg/day IV in 2–4 doses f

N/A

N/A

1.5 mg/kg q 36 h

Dalbavancin

N/A

1000 mg as a single dose, followed by a 500-mg dose 1 wk later

1000 mg as a single dose, followed by 500-mg dose 1 wk later

N/A

N/A

1000 mg as a single dose, followed by a 500-mg dose 1 wk later

Daptomycin

N/A

4–6 mg/kg IV q 24 h

8–10 mg/kg IV q 24 h f

N/A

N/A

4–6 mg/kg IV q 48 h

Fosfomycin

A single dose of 3 g in 3–4 oz of water

N/A in US

N/A

N/A

N/A

A single dose of 3 g in 3–4 oz of water

Linezolid

0.6 g q 12 h

0.6 g IV q 12 h

0.6 g IV q 12 h

10 mg/kg q 8 h

10 mg/kg IV q 8 h

0.6 g IV or po q 12 h

Metronidazole

For anaerobic infection

7.5 mg/kg q 6 h (not to exceed 4 g/day)

7.5 mg/kg IV q 6 h (not to exceed 4 g/day)

7.5 mg/kg IV q 6 h (not to exceed 4 g/day)

7.5 mg/kg q 6 h

7.5 mg/kg IV q 6 h

3.75 mg/kg IV or po q 6 h (not to exceed 2 g/day)

For trichomoniasis

2 g for 1 dose

or

0.5 g q 12 h for 7 days

N/A

N/A

N/A

N/A

N/A

For Clostridium difficile–induced diarrhea (pseudomembranous colitis)

0.5 g q 6–8 h for 10–14 days

500 mg IV q 6–8 h

500 mg IV q 6 h

7.5 mg/kg q 8 h

7.5 mg/kg IV q 6 h

250 mg po or IV q 8 h

For amebiasis

0.5–0.75 g q 8 h for 10 days followed by paromomycin po 0.5 g q 8 h for 7 days

0.75 g IV q 8 h for 10 days followed by paromomycin po 0.5 g q 8 h for 7 days

0.75 g IV q 8 h for 10 days followed by paromomycin po 0.5 g q 8 h for 7 days

11.6–16.6 mg/kg q 8 h for 7–10 days

11.6–16.6 mg/kg IV q 8 h for 7–10 days

N/A

For giardiasis

0.25 g q 6–8 h for 5–7 days

N/A

N/A

5 mg/kg q 6–8 h for 5 days

N/A

N/A

Nitrofurantoin macrocrystals

50–100 mg q 6 h

N/A

N/A

1.25–1.75 mg/kg q 6 h

N/A

Not recommended

Nitrofurantoin monohydrate/macrocrystals

100 mg q 12 h

N/A

N/A

N/A

N/A

N/A

Oritavancin

N/A

1200 mg as a single dose

1200 mg as a single dose

N/A

N/A

1200 mg as a single dose

Quinupristin/dalfopristin

N/A

7.5 mg/kg IV q 8–12 h

7.5 mg/kg IV q 8 h

N/A

7.5 mg/kg IV q 12 h for complicated skin or skin structure infection

or

7.5 mg/kg q 8 h for serious infections

7.5 mg/kg IV q 8–12 h

Rifampin b

For TB

0.6 g q 24 h

0.6 g IV q 24 h

N/A

5–10 mg/kg q 12 h

or

10–20 mg/kg q 24 h

10–20 mg/kg IV q 24 h

0.3–0.6 g IV or po q 24 h

For meningococcal exposure

0.6 g q 12 h for 4 doses

N/A

N/A

Age 1 mo: 10 mg/kg q 12 h for 2 days

Age < 1 mo: 5 mg/kg q 12 h for 2 days

N/A

0.6 g po q 12 h for 4 doses

For Haemophilus influenzae exposure

20 mg/kg q 24 h for 4 days (not to exceed 600 mg q 24 h)

N/A

N/A

20 mg/kg q 24 h for 4 days

Age < 1 mo: 10 mg/kg q 24 h for 4 days

N/A

20 mg/kg q 24 h for 4 days (not to exceed 600 mg q 24 h)

For staphylococcal infections (used with a penicillin, cephalosporin, or vancomycin)

0.3 g q 8 h

or

0.6–0.9 g q 24 h

0.3 g IV q 8 h

or

0.6–0.9 g IV q 24 h

0.3 g IV q 8 h

or

0.6–0.9 g IV q 24 h

0.3 g IV or po q 8 h

or

0.6–0.9 g IV or po q 24 h

Rifapentine

For pulmonary TB (as part of a 3- or 4- drug regimen)

Initial phase (2 mo): 0.6 g twice/wk

Continuation phase (4 mo): 0.6 g once/wk

N/A

N/A

N/A

N/A

N/A

For latent TB (in combination with isoniazid)

0.9 g once/wk (3 mo)

N/A

N/A

N/A

N/A

N/A

Tedizolid

200 mg q 24 h

200 mg IV q 24 h

200 mg IV q 24 h

N/A

N/A

200 mg po or IV q 24 h

Telavancin

N/A

10 mg/kg IV q 24 h

10 mg/kg IV q 24 h

N/A

N/A

N/A

Vancomycin

125 mg q 6 h (only effective for C. difficile–induced diarrhea

15 mg/kg IV q 12 h (often 1 g q 12)

15 mg/kg IV q 12 h

N/A

13 mg/kg IV q 8 h

or

10 mg/kg IV q 6 h

0.5–1.0 g IV q wk

For meningitis

N/A

1 g IV q 8 h

or

1.5 g IV q 12 h g

1 g IV q 8 h

or

1.5 g IV q 12 h

N/A

15 mg/kg IV q 6 h

15 mg/kg IV q wk

a Initial loading dose should be equivalent to the usual dose for patients with normal renal function, followed by a dose adjusted for renal failure. Dosing adjustments of aminoglycosides should be assisted by measuring peak (drawn 1 h after the start of a 30-min IV infusion) and trough (drawn 30 min before next dose) serum levels.

b Rate or extent of absorption is decreased when the drug is taken with food.

c Dosage should not exceed that for adults.

d These drugs are generally avoided in children.

e Dose is based on TMP.

f The standard of care for dosing of this antibiotic for serious infections is complex and rapidly evolving (see discussion of individual drug for a more information).

g In addition, intrathecal or intraventricular vancomycin 10–20 mg/day may be necessary, and dose may need to be adjusted to achieve trough CSF levels of 10–20 μg/mL.

N/A = not applicable; TMP = trimethoprim.


Duration

Antibiotics should be continued until objective evidence of systemic infection (eg, fever, symptoms, abnormal laboratory findings) is absent for several days. For some infections (eg, endocarditis, TB, osteomyelitis), antibiotics are continued for weeks or months to prevent relapse.


Complications

Complications of antibiotic therapy include superinfection by nonsusceptible bacteria or fungi and cutaneous, renal, hematologic, and GI adverse effects.

Adverse effects frequently require stopping the causative drug and substituting another antibiotic to which the bacteria are susceptible; sometimes, no alternatives exist.


Antibiotic Resistance

Resistance to an antibiotic may be inherent in a particular bacterial species or may be acquired through mutations or acquisition of genes for antibiotic resistance that are obtained from another organism. Different mechanisms for resistance are encoded by these genes (see Table: Common Mechanisms of Antibiotic Resistance). Resistance genes can be transmitted between 2 bacterial cells by the following mechanisms:

  • Transformation (uptake of naked DNA from another organism)

  • Transduction (infection by a bacteriophage)

  • Conjugation (exchange of genetic material in the form of either plasmids, which are pieces of independently replicating extrachromosomal DNA, or transposons, which are movable pieces of chromosomal DNA)

Plasmids and transposons can rapidly disseminate resistance genes.

Antibiotic use preferentially eliminates nonresistant bacteria, increasing the proportion of resistant bacteria that remain. Antibiotic use has this effect not only on pathogenic bacteria but also on normal flora; resistant normal flora can become a reservoir for resistance genes that can spread to pathogens.

Common Mechanisms of Antibiotic Resistance

Mechanism

Example

Decreased cell wall permeability

Loss of outer membrane D2 porin in imipenem-resistant Pseudomonas aeruginosa

Enzymatic inactivation

Production of β-lactamases that inactivate penicillins in penicillin-resistant Staphylococcus aureus, Haemophilus influenzae, and Escherichia coli

Production of aminoglycoside-inactivating enzymes in gentamicin-resistant enterococci

Changes in target

Decreased affinity of penicillin-binding proteins for β-lactam antibiotics (eg, in Streptococcus pneumoniae with reduced penicillin sensitivity)

Decreased affinity of methylated ribosomal RNA target for macrolides, clindamycin, and quinupristin in MLSB-resistant S. aureus

Decreased affinity of altered cell wall precursor for vancomycin (eg, in Enterococcus faecium)

Decreased affinity of DNA gyrase for fluoroquinolones in fluoroquinolone-resistant S. aureus

Increased antibiotic efflux pump

Increased efflux of tetracycline, macrolides, clindamycin, or fluoroquinolones (eg, in S. aureus)

Bypass of antibiotic inhibition

Development of bacterial mutants that can subsist on products (eg, thymidine) present in the environment, not just products synthesized within the bacteria (eg, in certain bacteria exposed to trimethoprim/sulfamethoxazole)

MLSB = macrolide, lincoside, streptogramin B.

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • NIZORAL
  • AVELOX
  • ACHROMYCIN V
  • LANOXIN
  • PERIOSTAT, VIBRAMYCIN
  • ERY-TAB, ERYTHROCIN
  • FLOXIN OTIC
  • RIFADIN, RIMACTANE
  • No US brand name
  • FLAGYL
  • ZITHROMAX
  • VANCOCIN
  • IQUIX, LEVAQUIN, QUIXIN
  • LANIAZID
  • CILOXAN, CIPRO
  • CLEOCIN
  • COUMADIN
  • KETEK
  • DILANTIN
  • BIAXIN
  • ZYVOX
  • ELIXOPHYLLIN
  • ROCEPHIN
  • CUBICIN
  • FURADANTIN, MACROBID, MACRODANTIN
  • BACTOCILL IN PLASTIC CONTAINER
  • MINOCIN
  • PRIFTIN
  • FACTIVE
  • MAXIPIME
  • FORTAZ, TAZICEF
  • NEO-FRADIN
  • GENOPTIC
  • DORIBAX
  • TYGACIL
  • MEFOXIN
  • MERREM
  • NALLPEN IN PLASTIC CONTAINER
  • AMOXIL
  • MYCOBUTIN
  • DIFICID
  • CEDAX
  • CLAFORAN
  • VIBATIV
  • NOROXIN
  • KEFLEX
  • MONUROL
  • CEFTIN, ZINACEF
  • ANCEF, KEFZOL
  • TOBI, TOBREX
  • INVANZ
  • AZACTAM

* This is a professional Version *