Merck Manual

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Overview of Antibacterial Drugs

By

Brian J. Werth

, PharmD, University of Washington School of Pharmacy

Last full review/revision May 2020| Content last modified May 2020
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Topic Resources

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 the following:

  • Inhibiting cell wall synthesis

  • Increasing cell membrane permeability

  • 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 Some 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.

Table
icon

Some Common Effects of Antibiotics on Other Drugs

Drug

Toxicity Enhanced By

No Change With

Digoxin

All macrolides (eg, azithromycin, clarithromycin, erythromycin)

Minocycline

Rifampin (decreased digoxin concentrations)

Tetracycline

Oxazolidinones (including tedizolid)

Phenytoin

Ciprofloxacin

Isoniazid

Some macrolides (erythromycin, clarithromycin, telithromycin)

Rifampin (decreased phenytoin levels)

Azithromycin

Aminoglycosides

Clindamycin

Doxycycline

Fluoroquinolones except ciprofloxacin

Linezolid

Metronidazole

Quinulpristine/dalfopristin

Trimethoprim

Vancomycin

Theophylline

Ciprofloxacin

Clarithromycin

Erythromycin

Rifampin (decreased theophylline levels)

Azithromycin

Doxycycline

Linezolid

Trimethoprim

Warfarin

Cefoperazone*

Cefotetan*

Clarithromycin

Doxycycline

Erythromycin

Certain fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin)

Rifampin (decreased prothrombin time)

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.

In general, clinicians should try to use antibiotics with the narrowest spectrum of activity and for the shortest duration.

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. Susceptibility data should be compiled into antibiograms and used to direct empiric treatment whenever possible. Antibiograms summarize regional facility–specific (or location–specific) antibiotic susceptibility patterns of common pathogens to commonly used antibiotics.

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 beta-lactam, vancomycin) plus an aminoglycoside.

Effectiveness

In vivo antibiotic effectiveness is affected by many factors, including

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. More precise quantitative methods identify the minimum in vitro concentration at which an antibiotic can inhibit growth (minimum inhibitory concentration [MIC]) or kill (minimum bactericidal concentration [MBC]). An antibiotic with bactericidal activity may improve bacterial killing when 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). However, there are limited clinical data indicating that a bactericidal drug should be selected over a bacteriostatic drug simply on the basis of that classification. Drug selection for optimal efficacy should be based on how the drug concentration varies over time in relation to the MIC rather than whether the drug has bactericidal or bacteriostatic activity.

Antibiotics can be grouped into 3 general categories (1) based on the pharmacokinetics that optimizes antimicrobial activity (pharmacodynamics):

  • Concentration-dependent: The magnitude by which the peak concentration exceeds the MIC (typically expressed as the peak-to-MIC ratio) best correlates with antimicrobial activity

  • Time-dependent: The duration of the dosing interval in which the antibiotic concentration exceeds the MIC (typically expressed as the percentage of time above MIC) best correlates with antimicrobial activity

  • Exposure-dependent: The amount of drug given relative to the MIC (the amount of drug is the 24-hour area under the concentration-time curve [AUC24]; the AUC24-to-MIC ratio best correlates with antimicrobial activity)

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 the rate and extent of their bactericidal activity. In addition, if concentrations exceed the MIC even briefly, aminoglycosides and fluoroquinolones have a post-antibiotic effect (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.

Beta-lactams, clarithromycin, and erythromycin 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 (ie, minimal post-antibiotic effect), beta-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 (about 8 hours), free serum levels exceed the MIC of very susceptible pathogens for the entire 24-hour dosing interval. However, for beta-lactams that have serum half-lives of 2 hours, frequent dosing or continuous infusion is required to optimize the time above the MIC.

Most antimicrobials have exposure-dependent antibacterial activity best characterized by the AUC-to-MIC ratio. Vancomycin, tetracyclines, and clindamycin are examples.

Time vs concentration of a single dose of a theoretical antibiotic

Time vs concentration of a single dose of a theoretical antibiotic

There are 3 pharmacokinetic/pharmacodynamic parameters related to antimicrobial efficacy:

  • Ratio of peak serum concentration to MIC

  • Percent time above MIC

  • Ratio of 24-hour AUC to MIC

Effectiveness reference

Route

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

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

  • Oral antibiotics are poorly absorbed (eg, because of malabsorption after intestinal surgery, impaired intestinal motility [eg, due to opioid use]).

  • Patients are critically ill, possibly impairing gastrointestinal 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:

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.

Table
icon

Usual Dosages of Commonly Prescribed Antibiotics[a]

Drug

Adult Dosage

Pediatric (Age > 1 Month) Dosage

Dosage in Renal Failure[b] (Creatinine Clearance < 10 mL/minute)

Oral

Parenteral

Serious Infections

Oral

Parenteral

Amikacin

N/A

15 mg/kg IV once/day

or

7.5 mg/kg every 12 hours

15 mg/kg IV once/day

or

7.5 mg/kg IV every 12 hours

N/A

5–7.5 mg/kg IV every 12 hours

1.5–2.5 mg/kg IV every 24–48 hours

Gentamicin

N/A

5–7 mg/kg IV once/day

or

1.7 mg/kg IV every 8 hours

5–7 mg/kg IV once/day

N/A

1–2.5 mg/kg IV every 8 hours

0.34–0.51 mg/kg IV every 24–48 hours

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

N/A

1 mg/kg IV every 8 hours

N/A

N/A

1 mg/kg IV every 8 hours

Infectious disease consultation required for dosage

Dosage adjusted to achieve peak serum concentration of 3–4 mcg/mL (6.3–8.4 micromol/L) and trough concentration of < 1 mcg/mL (2.1 micromol/L)

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 every 4 hours 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 4 times a day

N/A

N/A

0.6–1.75 g/m2 every 6 hours

or

0.4–1.2 g/m2 every 4 hours

N/A

N/A

Streptomycin

  • For tuberculosis

N/A

15 mg/kg IM every 24 hours (maximum: 1.0 g/day) initially, then 1.0 g 2–3 times/week

N/A

N/A

20–40 mg/kg IM once/day

7.5 mg/kg IM every 72–96 hours (maximum: 1 g)

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

N/A

7.5 mg/kg IM every 12 hours

N/A

N/A

N/A

N/A

Tobramycin

N/A

5–7 mg/kg IV once/day

or

1.7 mg/kg IV every 8 hours

5–7 mg/kg IV once/day

or

1.7 mg/kg IV every 8 hours

N/A

1–2.5 mg/kg IV every 8 hours

0.34–0.51 mg/kg IV every 24–48 hours

Beta-lactams: Cephalosporins (1st generation)

Cefadroxil

0.5–1 g every 12 hours

N/A

N/A

15 mg/kg every 12 hours

N/A

0.5 g orally every 36 hours

Cefazolin

N/A

1–2 g IV every 8 hours

2 g IV every 8 hours

N/A

16.6–33.3 mg/kg IV every 8 hours

1–2 g IV every 24–48 hours

Cephalexin

0.25–0.5 g every 6 hours

N/A

N/A

6.25–12.5 mg/kg every 6 hours

or

8.0–16 mg/kg every 8 hours

N/A

0.25–0.5 g orally every 24–48 hours

Beta-lactams: Cephalosporins (2nd generation)

Cefaclor[c]

0.25–0.5 g every 8 hours

N/A

N/A

10–20 mg/kg every 12 hours

or

6.6–13.3 mg/kg every 8 hours

N/A

0.5 g orally every 12 hours

Cefotetan

N/A

1–3 g IV every 12 hours

2–3 g IV every 12 hours

N/A

20–40 mg/kg IV every 12 hours

1–3 g IV every 48 hours

Cefoxitin

N/A

1 g IV every 8 hours to 2 g IV every 4 hours

2 g IV every 4 hours

or

3 g IV every 6 hours

N/A

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

0.5–1.0 g IV every 24–48 hours

Cefprozil

0.25 g every 12 hours

or

0.5 g every 12–24 hours

N/A

N/A

15 mg/kg every 12 hours for otitis media

N/A

0.25 g orally every 12–24 hours

Cefuroxime

0.125–0.5 g every 12 hours

0.75–1.5 g IV every 6–8 hours

1.5 g IV every 6 hours

10–15 mg/kg suspension every 12 hours

For older children: 125–250-mg tablets every 12 hours

25–50 mg/kg IV every 8 hours

0.25–0.5 g orally every 24 hours

or

0.75 g IV every 24 hours

  • For meningitis

3 g IV every 8 hours

50–60 mg/kg IV every 6 hours

Beta-lactams: Cephalosporins (3rd generation)

Cefotaxime

N/A

1 g every 12 hours to 2 g IV every 4 hours

2 g IV every 4 hours

N/A

8.3–33.3 mg/kg IV every 4 hours

or

16.6–66.6 mg/kg every 6 hours

1–2 g IV every 24 hours

Cefpodoxime[d]

0.1–0.4 g every 12 hours

N/A

N/A

5 mg/kg every 12 hours

N/A

0.1–0.4 g orally every 24 hours

Ceftazidime

N/A

1 g IV every 12 hours to 2 g every 8 hours

2 g IV every 8 hours

N/A

25–50 mg/kg IV every 8 hours

0.5 g IV every 24–48 hours

Ceftazidime/avibactam

(2.5 g = ceftazidime 2 g + avibactam 0.5 g)

N/A

2.5 g IV every 8 hours

2.5 g IV every 8 hours

N/A

N/A

0.94 g IV every 24–48 hours

Ceftibuten[c]

0.4 g every 24 hours

N/A

N/A

9 mg/kg once/day

N/A

0.1 g orally every 24 hours

Ceftriaxone

N/A

1–2 g IV every 24 hours

2 g IV every 24 hours

N/A

50–75 mg/kg IV every 24 hours

or

25–37.5 mg/kg every 12 hours

Same as adult dose

  • For meningitis

N/A

2 g IV every 12 hours

2 g IV every 12 hours

N/A

50 mg/kg IV every 12 hours or 100 mg/kg every 24 hours (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 every 12 hours

Beta-lactams: Cephalosporins (4th generation)

Cefepime

N/A

1–2 g IV every 8–12 hours

2 g IV every 8 hours

N/A

50 mg/kg IV every 8–12 hours

0.25–1 g IV every 24 hours

Beta-lactams: Cephalosporins (5th generation)

Ceftaroline

N/A

0.6 g IV every 12 hours

0.6 g IV every 12 hours

N/A

N/A

0.2 g IV every 12 hours

Ceftolozane/tazobactam

(1.5 g = ceftolozane 1 g + tazobactam 0.5 g)

N/A

1.5 g IV every 8 hours

1.5 g IV every 8 hours

N/A

N/A

0.75 g IV once, then 0.15 g IV every 8 hours

Cefiderocol

N/A

2 g IV every 8 hours

2 g IV every 8 hours

N/A

N/A

0.75 g IV every 12 hours

Beta-lactams: Penicillins

Amoxicillin

0.25–0.5 g every 8 hours

or

0.875 g every 12 hours

N/A

N/A

12.5–25 mg/kg every 12 hours

or

7–13 mg/kg every 8 hours

N/A

0.25–0.5 g orally every 24 hours

  • For endocarditis prophylaxis

2 g for 1 dose

N/A

N/A

50 mg/kg 1 hours before procedure

N/A

2 g orally for 1 dose

Amoxicillin/clavulanate

0.25–0.5 g every 8 hours

or

0.875 g every 12 hours

N/A

N/A

If > 40 kg: Adult dose

N/A

0.25–0.5 g orally every 24 hours

Amoxicillin/clavulanate, ES-600

N/A

N/A

N/A

45 mg/kg every 12 hours

N/A

N/A

Amoxicillin/clavulanate, extended-release

2 g every 12 hours

N/A

N/A

N/A

N/A

N/A

Ampicillin

N/A

0.5–2.0 g IV every 4–6 hours

2 g IV every 4 hours

N/A

25–50 mg/kg IV every 6 hours

0.5–2.0 g IV every 12–24 hours

  • For meningitis

N/A

2 g IV every 4 hours

2 g IV every 4 hours

N/A

50–100 mg/kg IV every 6 hours

2 g IV every 12 hours

Ampicillin/sulbactam

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

N/A

1.5–3.0 g IV every 6 hours

3 g IV every 6 hours

N/A

25–50 mg/kg IV every 6 hours

1.5–3.0 g IV every 24 hours

Dicloxacillin[c]

0.125–0.5 g every 6 hours

N/A

N/A

3.125–6.25 mg/kg every 6 hours

N/A

0.125–0.5 g orally every 6 hours

Nafcillin

Rarely used

1–2 g IV every 4 hours

2 g IV every 4 hours

N/A

12.5–25 mg/kg IV every 6 hours

or

8.3–33.3 mg/kg every 4 hours

1–2 g IV every 4 hours

Oxacillin

Rarely used

1–2 g IV every 4 hours

2 g IV every 4 hours

N/A

12.5–25 mg/kg IV every 6 hours

or

8.3–33.3 mg/kg IV every 4 hours

1–2 g IV every 4 hours

Penicillin G[c]

0.25–0.5 g every 6–12 hours (penicillin V)

1–4 million units IV every 4–6 hours

4 million units IV every 4 hours

Penicillin VK

6.25–12.5 mg/kg every 8 hours

6,250–100,000 units/kg IV every 6 hours

or

4,166.6–66,666 units/kg IV every 4 hours

0.5–2 million units IV every 4–6 hours (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 every 3–4 weeks

N/A

N/A

25,000–50,000 units/kg IM every 3–4 weeks

1.2 million units IM every 3–4 weeks

  • 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/week for 3 weeks

N/A

N/A

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

2.4 million units IM for 1 dose

Penicillin G procaine (IM only)

N/A

0.3–0.6 million units IM every 12 hours

N/A

N/A

25,000–50,000 units/kg IM every 24 hours

or

12,500–25,000 units/kg IM every 12 hours

0.3 to 0.6 million units IM every 12 hours

Piperacillin (1.9 mEq sodium/g)

N/A

3 g IV every 4–6 hours

3 g IV every 4 hours

N/A

50–75 mg/kg IV every 6 hours

or

33.3–50 mg/kg IV every 4 hours

3–4 g IV every 12 hours

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

N/A

3.375 g IV every 6 hours

3.375 g IV infused over 4 hours every 8 hours or 4.5 g IV every 6 hours

N/A

80 mg/kg IV every 8 hours

2.25 g IV every 8 hours to 4.5 g IV every 12 hours

Ticarcillin (5.2 mEq sodium/g)

N/A

3 g IV every 4–6 hours

3 g IV every 4 hours

N/A

If < 60 kg: 50 mg/kg IV every 4–6 hours

1–2 g IV every 12 hours

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

N/A

3.1 g IV every 4–6 hours

3.1 g IV every 4 hours

N/A

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

2 g IV every 12 hours

Beta-lactams: Monobactams

Aztreonam

N/A

1–2 g IV every 6–12 hours

2 g IV every 6 hours

N/A

30–40 mg/kg IV every 6–8 hours

0.5 g IV every 8 hours

Beta-lactams: Carbapenems

Ertapenem

N/A

1 g IV every 24 hours

1 g IV every 24 hours

N/A

N/A

0.5 g IV every 24 hours

Imipenem

N/A

0.5–1.0 g IV every 6 hours

1 g IV every 6 hours

N/A

For infants 4 weeks to 3 months: 25 mg/kg IV every 6 hours

For children >3 months: 15–25 mg/kg IV every 6 hours

0.125–0.25 g IV every 12 hours (may increase risk of seizures)

Meropenem

N/A

1 g IV every 8 hours

2 g IV every 8 hours

N/A

20–40 mg/kg IV every 8 hours

0.5 g IV every 24 hours

  • For meningitis

N/A

2g IV every 8 hours

2 g IV every 8 hours

N/A

40 mg/kg IV every 8 hours

1 g IV every 24 hours

Meropenem/vaborbactam (4 g = meropenem 2 g + vaborbactam 2 g)

N/A

4 g IV every 8 hours

4 g IV every 8 hours

N/A

N/A

1g IV every 12 hours

Doripenem

N/A

0.5 g IV every 8 hours

0.5 g IV every 8 hours

N/A

N/A

0.25 g IV every 24 hours

Ciprofloxacin

0.5–0.75 g every 12 hours

0.2–0.4 g IV every 8–12 hours

0.4 g IV every 8 hours

10–15 mg/kg IV every 12 hours (in select circumstances)

10–15 mg/kg IV every 12 hours (in select circumstances)

0.5–0.75 g orally every 24 hours

or

0.2–0.4 g IV every 24 hours

  • Extended-release for uncomplicated cystitis

0.5 g every 24 hours for 3 days

N/A

N/A

N/A

N/A

N/A

Delafloxacin

450 mg every 12 hours

300 mg IV every 12 hours

300 mg IV every 12 hours

N/A

N/A

N/A

Gemifloxacin

320 mg every 24 hours

N/A

N/A

N/A

N/A

160 mg orally every 24 hours

Levofloxacin

0.25–0.75 g every 24 hours

0.25–0.75 IV g every 24 hours

0.75 g IV every 24 hours

N/A

N/A

0.25–0.5 g orally or IV every 48 hours

Moxifloxacin

0.4 g every 24 hours

0.4 g IV every 24 hours

0.4 g IV every 24 hours

N/A

N/A

0.4 g every 24 hours orally or IV

Norfloxacin[c]

0.4 g every 12 hours

N/A

N/A

N/A

N/A

0.4 g orally every 24 hours

Ofloxacin

0.2–0.4 g every 12 hours

0.4 g IV every 12 hours

0.2–0.4 g IV every 12 hours

N/A

N/A

0.1–0.2 g orally or IV every 24 hours

Azithromycin

0.5 g on day 1, then 0.25 g every 24 hours for 4 days

0.5 g IV every 24 hours

0.5 g IV every 24 hours

N/A

0.5 g orally on day 1, then 0.25 g orally every 24 hours for 4 days or 0.5 g IV every 24 hours

  • 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 1 dose

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 every 12 hours

Extended-release: 1 g every 24 hours

N/A

N/A

7.5 mg/kg every 12 hours

N/A

0.25–0.5 g orally every 24 hours

Erythromycin base[c]

0.25–0.5 g every 6 hours

N/A

N/A

10–16.6 mg/kg every 8 hours

or

7.5–12.5 mg/kg every 6 hours

N/A

0.25 g orally every 6 hours

  • For gastrointestinal preoperative bowel preparation

1 g for 3 doses

N/A

N/A

20 mg/kg for 3 doses

N/A

N/A

Erythromycin lactobionate

N/A

0.5–1 g IV every 6 hours

1 g IV every 6 hours

N/A

3.75–5.0 mg/kg IV every 6 hours

0.5 g IV every 6 hours

Erythromycin gluceptate

N/A

0.5–1 g IV every 6 hours

1 g IV every 6 hours

N/A

3.75–5.0 mg/kg IV every 6 hours

0.5 g IV every 6 hours

Fidaxomycin for Clostridioides difficile (formerly Clostridium difficile) infection

200 mg 2 times a day for 10 days

N/A

N/A

Weight-based dosing for infants ≥ 6 months and children:

  • 16 mg/kg 2 times a day for 10 days; maximum: 200 mg/dose

Fixed dosing for infants ≥ 6 months, children, and adolescents:

  • 4 to < 7 kg, oral suspension: 80 mg 2 times a day for 10 days

  • 7 to < 9 kg, oral suspension: 120 mg 2 times a day for 10 days

  • 9 to < 12.5 kg, oral suspension: 160 mg 2 times a day for 10 days

  • ≥ 12.5 kg, oral suspension, tablets: 200 mg 2 times a day for 10 days

N/A

N/A (minimal systemic absorption)

Sulfisoxazole

1.0 g every 6 hours

25 mg/kg IV every 6 hours (not available in the US)

N/A

30–37.5 mg/kg every 6 hours

or

20–25 mg/kg every 4 hours

N/A

1 g orally every 12–24 hours

Sulfamethizole

0.5–1 g every 6–8 hours

N/A

N/A

7.5–11.25 mg/kg every 6 hours

N/A

N/A

Sulfamethoxazole

1 g every 8–12 hours

N/A

N/A

25–30 mg/kg every 12 hours

N/A

1 g orally every 24 hours

Trimethoprim

0.1 g every 12 hours

or

0.2 g every 24 hours

N/A

N/A

2 mg/kg every 12 hours for 10 days for urinary tract infection

N/A

0.1 g orally every 24 hours

Trimethoprim/sulfamethoxazole[f]

0.16/0.8 g every 12 hours

3–5 mg TMP/kg IV every 6–8 hours

5 mg TMP/kg IV every 6 hours

3–6 mg TMP/kg every 12 hours

3–6 mg TMP/kg IV every 12 hours

Not recommended if other alternatives are available

  • For Pneumocystis jirovecii pneumonia[f]

0.32/1.6 g every 8 hours for 21 days

5 mg TMP/kg IV every 8 hours for 21 days

5 mg TMP/kg IV every 6–8 hours

5–6.6 mg TMP/kg every 8 hours

or

3.75–5 mg TMP/kg every 6 hours

5–6.6 mg TMP/kg IV every 8 hours

or

3.75–5 mg TMP/kg IV every 6 hours

If essential, 5 mg TMP/kg IV every 24 hours

or

1.25 mg TMP/kg IV every 6 hours

Doxycycline

0.1 g every 12 hours

0.1 g IV every 12 hours

0.1 mg IV every 12 hours

Age > 8 years: 2–4 mg/kg every 24 hours

or

1–2 mg/kg every 12 hours

Age > 8 years: 2–4 mg/kg IV every 24 hours

or

1–2 mg/kg IV every 12 hours

0.1 g IV or orally every 12 hours

Eravacycline

N/A

1 mg/kg IV every 12 hours

Same as adult dose

N/A

N/A

Same as adult dose

Minocycline

0.1 g every 12 hours

0.1 g IV every 12 hours

0.1 g IV every 12 hours

N/A

N/A

0.1 g IV or orally every 12 hours

Omadacycline

0.45 g every 24 hours x 2 doses, then 0.3 g every 24 hours

0.2 g IV on day 1, then 0.1 g IV every 24 hours

Same as adult dose

N/A

N/A

Same as adult dose

Tetracycline[c]

0.25–0.5 g every 6 hours

N/A

N/A

Age > 8 years: 6.25–12.5 mg/kg every 6 hours

N/A

Doxycycline used instead

Tigecycline

N/A

100 mg, then 50 mg (25 mg for severe hepatic dysfunction) IV every 12 hours

Same as adult dose[g]

N/A

N/A

Same as adult dose

Others

Clindamycin

0.15–0.45 g every 6 hours

0.6 g IV every 6 hours to 0.9 IV g every 8 hours

0.9 g IV every 8 hours

2.6–6.6 mg/kg every 8 hours

or

2–5 mg/kg every 6 hours

6.6–13.2 mg/kg IV every 8 hours

or

5–10 mg/kg IV every 6 hours

0.15–0.45 g orally every 6 hours

or

0.6–0.9 g IV every 6–8 hours

Chloramphenicol

0.25–1 g every 6 hours

0.25–1.0 g IV every 6 hours

1 g IV every 6 hours

N/A

12.5–18.75 mg/kg IV every 6 hours

0.25–1.0 g IV every 6 hours

  • For meningitis

N/A

12.5 mg/kg every 6 hours (maximum: 4 g/day)

12.5 mg/kg IV every 6 hours (maximum: 4 g/day)

N/A

18.75–25 mg/kg IV every 6 hours

12.5 mg/kg IV every 6 hours (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[g]

N/A

N/A

1.5 mg/kg every 36 hours

Dalbavancin

N/A

1500 mg as a single dose or 1000 mg once, followed by a 500-mg dose 1 week later

1500 mg as a single dose or 1000 mg once, followed by a 500-mg dose 1 week later

N/A

N/A

1125 mg as a single dose or 750 mg once, followed by a 375-mg dose 1 week later

Daptomycin

N/A

4–6 mg/kg IV every 24 hours

8–10 mg/kg IV every 24 hours[g]

N/A

N/A

4–6 mg/kg IV every 48 hours

Fidaxomicin

0.2 g every 12 hours

N/A

N/A

N/A

N/A

0.2 g orally every 12 hours

Fosfomycin

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

Not available in the US

N/A

N/A

N/A

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

Lefamulin

0.6 g every 12 hours

0.15 g IV every 12 hours

Same as adult dose

N/A

N/A

Same as adult dose

Linezolid

0.6 g every 12 hours

0.6 g IV every 12 hours

0.6 g IV every 12 hours

10 mg/kg every 8 hours

10 mg/kg IV every 8 hours

0.6 g IV or orally every 12 hours

  • For anaerobic infection

7.5 mg/kg every 6 hours (not to exceed 4 g/day)

7.5 mg/kg IV every 6 hours (not to exceed 4 g/day)

7.5 mg/kg IV every 6 hours (not to exceed 4 g/day)

7.5 mg/kg every 6 hours

7.5 mg/kg IV every 6 hours

3.75 mg/kg IV or orally every 6 hours (not to exceed 2 g/day)

  • For trichomoniasis

2 g for 1 dose

or

0.5 g every 12 hours for 7 days

N/A

N/A

N/A

N/A

N/A

  • For Clostridioides difficile–induced diarrhea (pseudomembranous colitis)

0.5 g every 6–8 hours for 10–14 days

500 mg IV every 6–8 hours

500 mg IV every 6 hours

7.5 mg/kg every 8 hours

7.5 mg/kg IV every 6 hours

250 mg orally or IV every 8 hours

  • For amebiasis

0.5–0.75 g every 8 hours for 10 days followed by paromomycin orally 0.5 g every 8 hours for 7 days

0.75 g IV every 8 hours for 10 days followed by paromomycin orally 0.5 g every 8 hours for 7 days

0.75 g IV every 8 hours for 10 days followed by paromomycin orally 0.5 g every 8 hours for 7 days

11.6–16.6 mg/kg every 8 hours for 7–10 days

11.6–16.6 mg/kg IV every 8 hours for 7–10 days

N/A

  • For giardiasis

0.25 g every 6–8 hours for 5–7 days

N/A

N/A

5 mg/kg every 6–8 hours for 5 days

N/A

N/A

Nitrofurantoin macrocrystals

50–100 mg every 6 hours

N/A

N/A

1.25–1.75 mg/kg every 6 hours

N/A

Not recommended

Nitrofurantoin monohydrate/macrocrystals

100 mg every 12 hours

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 every 8–12 hours

7.5 mg/kg IV every 8 hours

N/A

7.5 mg/kg IV every 12 hours for complicated skin or skin structure infection

or

7.5 mg/kg every 8 hours for serious infections

7.5 mg/kg IV every 8–12 hours

Rifampin[c]

  • For tuberculosis (as part of a 3- or 4-drug regimen)

0.6 g every 24 hours

0.6 g IV every 24 hours

N/A

5–10 mg/kg every 12 hours

or

10–20 mg/kg every 24 hours

10–20 mg/kg IV every 24 hours

0.3–0.6 g IV or orally every 24 hours

  • For meningococcal exposure

0.6 g every 12 hours for 4 doses

N/A

N/A

Age 1 month: 10 mg/kg every 12 hours for 2 days

Age < 1 month: 5 mg/kg every 12 hours for 2 days

N/A

0.6 g orally every 12 hours for 4 doses

  • For Haemophilus influenzae exposure

20 mg/kg every 24 hours for 4 days (not to exceed 600 mg every 24 hours)

N/A

N/A

20 mg/kg every 24 hours for 4 days

Age < 1 month: 10 mg/kg every 24 hours for 4 days

N/A

20 mg/kg every 24 hours for 4 days (not to exceed 600 mg every 24 hours)

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

0.3 g every 8 hours

or

0.6–0.9 g every 24 hours

0.3 g IV every 8 hours

or

0.6–0.9 g IV every 24 hours

0.3 g IV every 8 hours

or

0.6–0.9 g IV every 24 hours

0.3 g IV or orally every 8 hours

or

0.6–0.9 g IV or orally every 24 hours

Rifapentine

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

Initial phase (2 months): 0.6 g twice/week

Continuation phase (4 months): 0.6 g once/week

N/A

N/A

N/A

N/A

N/A

  • For latent tuberculosis (in combination with isoniazid)

0.9 g once/week (3 months)

N/A

N/A

N/A

N/A

N/A

Tedizolid

200 mg every 24 hours

200 mg IV every 24 hours

200 mg IV every 24 hours

N/A

N/A

200 mg orally or IV every 24 hours

Telavancin

N/A

10 mg/kg IV every 24 hours

10 mg/kg IV every 24 hours

N/A

N/A

N/A

Vancomycin

125 mg every 6 hours (only effective for C. difficile–induced diarrhea)

15 mg/kg IV every 12 hours (often 1 g every 12)

25 mg/kg once, then 15–20 mg/kg IV every 8–12 hours[g]

N/A

13 mg/kg IV every 8 hours

or

10 mg/kg IV every 6 hours

0.5–1.0 g IV every week[h]

  • For meningitis[i]

N/A

N/A

15–20 mg/kg IV every 8–12 hours[h]

N/A

15 mg/kg IV every 6 hours

15 mg/kg IV every week[h]

[b] 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 hour after the start of a 30-minute IV infusion) and trough (drawn 30 minutes before next dose) serum levels.

[c] Rate or extent of absorption is decreased when the drug is taken with food.

[d] Dosage should not exceed that for adults.

[e] These drugs are generally avoided in children.

[f] Dose is based on TMP.

[g] 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).

[h] Doses should be adjusted to achieve a steady-state trough concentration of 15–20 mg/L. When technically possible, it is preferable to adjust doses using AUC24/MIC ratio.

[i] In addition, intrathecal or intraventricular vancomycin 10–20 mg/day may be necessary, and dose may need to be adjusted to achieve trough cerebrospinal fluid levels of 10–20 mcg/mL.

AUC24 = 24-hour area under the concentration-time curve; MIC = minimum inhibitory concentration; 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, tuberculosis, osteomyelitis, leprosy), 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, neurologic, and gastrointestinal 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.

Table
icon

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 beta-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 beta-lactam antibiotics (eg, in methicillin-resistant Staphylococcus aureus [MRSA] and 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.

Drugs Mentioned In This Article

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