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.”
(See also Antibiotics in Neonates.)
Antibiotics have many mechanisms of action, including the following:
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.
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 |
Beta-lactams (including carbapenems, cephalosporins, and penicillins) 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
-
Pharmacokinetics: The time course of antibiotic levels, which are affected by factors such as absorption, distribution (concentration in fluids and tissues, protein binding), rate of metabolism, and excretion
-
Pharmacodynamics: The antimicrobial activity of local antibiotic concentrations on the target pathogen and that pathogen's response including resistance
-
Presence of foreign materials
-
Control of source of infection
-
Drug interactions or inhibiting substances
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.
Effectiveness reference
-
1. A PK/PD Approach to Antibiotic Therapy. RxKinetics. Accessed 3/26/20.
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:
-
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)
-
Obese patients
-
Patients with cystic fibrosis
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 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 |
|
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 |
||||||
|
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 |
|
|
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 |
||||||
|
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) |
|
|
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 |
|
— |
— |
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 |
|
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 |
|
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 |
|
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) |
||||||
|
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 |
|
|
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 |
|
|
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 |
|
|
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 |
|
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 |
|
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 |
|
1 g for 1 dose |
N/A |
N/A |
N/A |
N/A |
N/A |
|
|
1 g for 1 dose |
N/A |
N/A |
5–10 mg/kg for 1 dose |
N/A |
N/A |
|
|
N/A |
N/A |
N/A |
12 mg/kg for 5 days |
N/A |
N/A |
|
|
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 |
|
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: Fixed dosing for infants ≥ 6 months, children, and adolescents: |
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 |
|
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 |
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|
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 |
|
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 |
|
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) |
|
|
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 |
|
|
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 |
|
|
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 |
|
|
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] |
||||||
|
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 |
|
|
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 |
|
|
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) |
|
|
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 |
||||||
|
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 |
|
|
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] |
|
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. |
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|
[d] Dosage should not exceed that for adults. |
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|
[e] These drugs are generally avoided in children. |
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|
[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. |
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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.
