Once-daily Dosing of Aminoglycosides Review and Recommendations for Clinical Practice
Aminoglycosides: A Practical Review
Am Fam Physician. 1998 Nov 15;58(8):1811-1820.
Related Editorial
Article Sections
- Abstract
- Pharmacology
- Clinical Uses
- Drug Resistance
- Drug Interactions and Adverse Effects
- Single vs. Multiple Daily Doses
- Cost
- References
Aminoglycosides are potent bactericidal antibiotics that act past creating fissures in the outer membrane of the bacterial cell. They are specially active against aerobic, gram-negative leaner and deed synergistically against sure gram-positive organisms. Gentamicin is the most commonly used aminoglycoside, just amikacin may be particularly constructive confronting resistant organisms. Aminoglycosides are used in the treatment of severe infections of the abdomen and urinary tract, equally well as bacteremia and endocarditis. They are also used for prophylaxis, especially confronting endocarditis. Resistance is rare but increasing in frequency. Avoiding prolonged use, volume depletion and concomitant administration of other potentially nephrotoxic agents decreases the chance of toxicity. Single daily dosing of aminoglycosides is possible considering of their rapid concentration-dependent killing and post-antibody effect and has the potential for decreased toxicity. Unmarried daily dosing of aminoglycosides appears to exist condom, efficacious and cost effective. In certain clinical situations, such every bit patients with endocarditis or pediatric patients, traditional multiple dosing is still commonly recommended.
The first aminoglycoside, streptomycin, was isolated from Streptomyces griseus in 1943. Neomycin, isolated from Streptomyces fradiae, had better activity than streptomycin against aerobic gram-negative bacilli but, because of its formidable toxicity, could not safely be used systemically. Gentamicin, isolated from Micromonospora in 1963, was a quantum in the handling of gram-negative bacillary infections, including those caused by Pseudomonas aeruginosa. Other aminoglycosides were subsequently developed, including amikacin (Amikin), netilmicin (Netromycin) and tobramycin (Nebcin), which are all currently available for systemic utilise in the Us.i
The purpose of this commodity is to provide family physicians with a review of the aminoglycosides and their office in the treatment of infectious diseases. Despite the introduction of newer, less toxic antimicrobial agents, aminoglycosides continue to serve a useful role in the treatment of serious enterococcal and gram-negative bacillary infections.
Pharmacology
- Abstruse
- Pharmacology
- Clinical Uses
- Drug Resistance
- Drug Interactions and Agin Effects
- Single vs. Multiple Daily Doses
- Price
- References
Traditionally, the antibacterial properties of aminoglycosides were believed to outcome from inhibition of bacterial protein synthesis through irreversible binding to the 30S bacterial ribosome. This explanation, even so, does non account for the potent bactericidal properties of these agents, since other antibiotics that inhibit the synthesis of proteins (such as tetracycline) are not bactericidal. Recent experimental studies show that the initial site of activity is the outer bacterial membrane. The cationic antibody molecules create fissures in the outer cell membrane, resulting in leakage of intracellular contents and enhanced antibiotic uptake. This rapid action at the outer membrane probably accounts for most of the bactericidal activity.ii Energy is needed for aminoglycoside uptake into the bacterial cell. Anaerobes have less energy bachelor for this uptake, so aminoglycosides are less agile against anaerobes.
Aminoglycosides are poorly absorbed from the gastrointestinal tract. After parenteral administration, aminoglycosides are primarily distributed within the extracellular fluid. Thus, the presence of disease states or iatrogenic situations that alter fluid residue may necessitate dosage modifications. When used parenterally, acceptable drug concentrations are typically institute in bone, synovial fluid and peritoneal fluid. Penetration of biologic membranes is poor because of the drug's polar construction, and intracellular concentrations are usually depression, with the exception of the proximal renal tubule. Endotracheal administration results in higher bronchial levels compared with systemic assistants, just differences in clinical event have not been consistent.
Following parenteral administration of an aminoglycoside, subtherapeutic concentrations are usually found in the cerebrospinal fluid, vitreous fluid, prostate and brain.three,4 Aminoglycosides are rapidly excreted past glomerular filtration, resulting in a plasma half-life varying from ii hours in a patient with "normal"renal function to 30 to 60 hours in patients who are functionally anephric.5 The half-life of aminoglycosides in the renal cortex is approximately 100 hours, so repetitive dosing may effect in renal aggregating and toxicity.
Clinical Uses
- Abstract
- Pharmacology
- Clinical Uses
- Drug Resistance
- Drug Interactions and Adverse Effects
- Unmarried vs. Multiple Daily Doses
- Toll
- References
Aminoglycosides display bactericidal, concentration-dependent killing activity and are active confronting a broad range of aerobic gram-negative bacilli. They are also agile against staphylococci and certain mycobacteria. Aminoglycosides are effective even when the bacterial inoculum is big, and resistance rarely develops during the course of treatment. These potent antimicrobials are used every bit prophylaxis and treatment in a variety of clinical situations5 (Table ane).
Table 1
Common Clinical Uses of Aminoglycosides*
| Serious, life-threatening gram-negative infection |
| Complicated skin, bone or soft tissue infection |
| Complicated urinary tract infection |
| Septicemia |
| Peritonitis and other astringent intra-abdominal infections |
| Severe pelvic inflammatory disease |
| Endocarditis |
| Mycobacterium infection |
| Neonatal sepsis |
| Ocular infections (topical) |
| Otitis externa (topical) |
Gentamicin is the aminoglycoside used most often because of its low toll and reliable activity confronting gram-negative aerobes. However, local resistance patterns should influence the choice of therapy. In general, gentamicin, tobramycin and amikacin are used in like circumstances, often interchangeably.4
Tobramycin may be the aminoglycoside of choice for use against P. aeruginosa because it has shown greater in vitro activeness. Yet, the clinical significance of this activity has been questioned.ane Amikacin is particularly effective when used against bacteria that are resistant to other aminoglycosides, since its chemical construction makes it less susceptible to inactivating enzymes.4 Depending on local patterns of resistance, amikacin may be the preferred agent for serious nosocomial infections acquired by gram-negative bacilli. Table 2 lists the price of diverse antibiotics used to treat gram-negative infections.
TABLE 2
Toll Comparison of Antibiotics Used for Treatment of Gram-Negative Infections
| Drug | Intravenous regimen | Price* |
|---|---|---|
| Amikacin (Amikin) | ane g daily | $ 65.00 |
| Aztreonam (Azactam) | 1 one thousand every 8 hours | 49.00 |
| 2 g every 8 hours | 65.l | |
| Ceftazidime (Fortaz) | 1 g every 8 hours | 44.00 |
| 2 m every 8 hours | 86.50 | |
| Ceftriaxone (Rocephin)† | 2 k daily | 72.50 |
| Cefotaxime (Claforan)† | 1 g every 8 hours | 33.50 |
| Ciprofloxacin (Cipro) | 400 mg every 12 hours | 57.50 |
| Gentamicin | 400 mg daily | 5.00 (per 80 mg) |
| Imipenem-cilastatin (Primaxin) | 500 mg every 6 hours | 109.00 |
| Levofloxacin (Levoquin)‡ | 500 mg daily | 39.50 |
| Piperacillin-tazobactam (Zosyn) | 3.375 thou every 6 hours | 61.00 |
| Ticarcillin-clavulanate (Timentin) | 3.i g every half-dozen hours | 58.00 |
| Tobramycin (Nebcin) | 400 mg daily | 7.00 (per 80-mg vial) |
| Trimethoprim-sulfamethoxazole (Bactrim)‡ | 10 mL (160 mg/800 mg) every 12 hours | 32.00 |
Drug Resistance
- Abstract
- Pharmacology
- Clinical Uses
- Drug Resistance
- Drug Interactions and Adverse Effects
- Single vs. Multiple Daily Doses
- Price
- References
Near resistance to aminoglycosides is acquired by bacterial inactivation by intracellular enzymes. Considering of structural differences, amikacin is non inactivated past the mutual enzymes that inactivate gentamicin and tobramycin. Therefore, a large proportion of the gram-negative aerobes that are resistant to gentamicin and tobramycin are sensitive to amikacin. In add-on, with increased utilize of amikacin, a lower incidence of resistance has been observed compared with increased use of gentamicin and tobramycin.5
P. aeruginosa may show adaptive resistance to aminoglycosides. This occurs when formerly susceptible populations get less susceptible to the antibiotic as a result of decreased intra-cellular concentrations of the antibody. This decrease may result in colonization, slow clinical response or failure of the antibody despite sensitivity on in vitro testing.six
Aminoglycosides are often combined with a beta-lactam drug in the treatment of Staphylococcus aureus infection. This combination enhances bactericidal activity, whereas aminoglycoside monotherapy may allow resistant staphylococci to persist during therapy and cause a clinical relapse once the antibiotic is discontinued.ane
Infective endocarditis that is due to enterococci with high levels of resistance to aminoglycosides is becoming increasingly mutual. All enterococci have low-level resistance to aminoglycosides because of their anaerobic metabolism. In the treatment of bacterial endocarditis, a beta-lactam drug is also used synergistically to facilitate aminoglycoside penetration into the cell. When high-level resistance occurs, it is typically due to the product of inactivating enzymes by the bacteria. Because of the increasing frequency of this resistance, all enterococci should be tested for antibody susceptibility.7
As with all antibiotics, resistance to aminoglycosides is becoming increasingly prevalent. Repeated use of aminoglycosides, especially when merely one type is employed, leads to an increased incidence of resistance.8 Nevertheless, resistance to aminoglycosides requires long periods of exposure or very big inocula of organisms and occurs less frequently than with other agents, such as third-generation cephalosporins, which are too effective confronting gram-negative organisms.1
Drug Interactions and Adverse Effects
- Abstract
- Pharmacology
- Clinical Uses
- Drug Resistance
- Drug Interactions and Agin Furnishings
- Unmarried vs. Multiple Daily Doses
- Toll
- References
Because the body does not metabolize aminoglycosides, aminoglycoside activity is unchanged by induction or inhibition of metabolic enzymes, such as those in the cytochrome P450 system. Certain medications may increment the risk of renal toxicity with aminoglycoside use (Table 3).
Table 3
Risk Factors Predisposing to Aminoglycoside Nephrotoxicity
| Potentially alterable factors |
| Apply of diuretics* |
| Radiographic dissimilarity exposure |
| Constructive circulating volume depletion |
| Use of ACE inhibitors† |
| Use of NSAIDs† |
| Use of other nephrotoxic medications |
| Concomitant use of amphotericin (Fungizone IV) |
| Utilize of cisplatin (Platinol) |
| Unalterable factors |
| Age |
| Pre-existing renal disease |
The toxicities of aminoglycosides include nephrotoxicity, ototoxicity (vestibular and auditory) and, rarely, neuromuscular occludent and hypersensitivity reactions. Nephrotoxicity receives the well-nigh attending, perhaps because of easier documentation of reduced renal part, but information technology is ordinarily reversible.
Ototoxicity is commonly irreversible. Originally, ototoxicity was believed to result from transiently high peak serum concentrations, resulting in a high concentration of drug in the inner ear. Recent studies in animal models have indicated that aminoglycoside accumulation in the ear is dose-dependent but saturable. In one case a threshold concentration of the antibiotic has been reached, increasing the drug concentration results in no further uptake. Experimental studies have shown increased drug accumulation by the cochlear organ of Corti with continuous infusion versus intermittent 30- to 60-minute infusions of aminoglycosides.9
Nephrotoxicity results from renal cortical accumulation resulting in tubular jail cell degeneration and sloughing. Examination of urine sediment may reveal dark-brownish, fine or granulated casts consistent with astute tubular necrosis but non specific for aminoglycoside renal toxicity.10 Although serum creatinine levels are ofttimes monitored during aminoglycoside use, an top of serum creatinine is more likely to reflect glomerular damage rather than tubular harm. In most clinical trials of aminoglycosides, however, nephrotoxicity has been defined by an summit of serum creatinine.five Periodic monitoring of serum creatinine concentrations may alert the clinician to renal toxicity.
In club to minimize toxicity, family physicians should remember a few fundamental considerations. (one) Aminoglycosides should be used but when their unique antibody dominance is needed, such as handling of infection in critically sick patients, and in nosocomial infections or infections with organisms resistant to less toxic therapies. (2) The clinician should change to a potentially less toxic antibiotic as soon as the infecting organism and its antibiotic sensitivities take been adamant. (iii) Potential chance factors that predispose to nephrotoxicity should be identified and, when possible, corrected (Table three).
Single vs. Multiple Daily Doses
- Abstract
- Pharmacology
- Clinical Uses
- Drug Resistance
- Drug Interactions and Adverse Furnishings
- Single vs. Multiple Daily Doses
- Cost
- References
Aminoglycoside antibiotics exhibit rapid concentration-dependent killing action.v,xi Increasing concentrations with college dosages increases both the charge per unit and the extent of bacterial prison cell decease. In addition, aminoglycosides have demonstrated persistent suppression of bacterial growth after brusque exposure, a response referred to as the post-antibiotic effect.five,12 The mail service-antibody effect is defined as the time required for an organism to demonstrate viable regrowth following the removal of an antibiotic.
The college the aminoglycoside dosage, the greater the post-antibiotic effect, upward to a certain maximal response. In vivo, the post-antibiotic effect for aminoglycosides is prolonged by the synergistic outcome of host leukocyte activeness. It is believed that leukocytes have enhanced phagocytosis and killing activity afterward exposure to aminoglycosides.thirteen
The previously mentioned principles and the singled-out differences in antimicrobial activeness between aminoglycosides and other anti-infectives provide support for the development of novel dosing schemes. A number of neutropenic and nonneutropenic animal models of infection accept been used to evaluate once-daily dosing of aminoglycosides. Demonstrated antibacterial efficacy and the potential for reduced toxicity prompted investigators to recommend the study of single daily dosing of aminoglycosides in the treatment of human infections.14
Another area of interest related to single daily dosing of aminoglycosides is cyclic variation in glomerular filtration. Glomerular filtration rates are lower in humans during the residue menstruation (midnight to 7:xxx a.g.). A study from a recently published nonrandomized, unblinded study showed a higher incidence of nephrotoxicity when aminoglycosides were administered during the rest catamenia.fifteen Thus, the upshot of varying time of aminoglycoside administration besides requires further report.
Currently, human being trial designs have included pharmacokinetic assessments, non-comparative trials involving single daily dosing regimens and comparative clinical trials to back up the concept of unmarried daily dosing.16 Unfortunately, the question of clinical superiority of unmarried daily dosing versus multiple daily dosing remains unanswered because of a lack of sufficient statistical power in the studies published to date. To address these shortcomings, seven meta-analyses comparing unmarried daily with multiple daily regimens have been published (Tabular array iv).17–23
Tabular array 4
Meta-Analyses Comparison Multiple Daily Dosing vs. Single Daily Dosing Regimens of Aminoglycosides
| Study | Studies reviewed | Studies included | Clinical response | Nephrotoxicity | Ototoxicity |
|---|---|---|---|---|---|
| Galloe, et al.17 | Unknown | 16 | ND | ND | ND |
| Hatala, et al.18 | 6 | 4 | ND | Tendency favoring SDD | Trend favoring SDD |
| Ali, et al.19 | 40 | 26 | SDD better | ND | ND |
| Bailey, et al.20 | Unknown | 20 | SDD better | ND | ND |
| Hatala, et al.21 | 42 | 17 | * | Trend favoring SDD | Trend favoring SDD |
| Freeman, et al.22 | 35 | 15 | † | SDD better | Not studied |
| Ferriols-Lisart, et al.23 | 67 | xviii | SDD meliorate | SDD better | ND |
Combining information from studies using meta-analytical techniques assumes that the differences among studies are due to chance. In addition, the choice of meta-analytic method and selection of data tin atomic number 82 to differing conclusions regarding the safety and efficacy of aminoglycosides. Withal, our goal is to present a review of both multiple and single daily dosing in various patient populations. Despite methodologic flaws in the available literature, current show would suggest that when single and multiple daily dosing regimens are compared there is no deviation in efficacy, and there is a trend toward reduced toxicity with the single regimens.
Tables 5 through 8 outline the dosing and monitoring of single and multiple daily dosing aminoglycoside regimens.24–27 It is important to note that single daily dosing is not currently recommended for use in pediatric patients or patients with cystic fibrosis, burns, enterococcal infection or bacterial endocarditis. Tabular array ix27 outlines aminoglycoside dosing regimens for endocarditis, and Table 10 gives pediatric dosing regimens. Dosing for premature infants differs from that of other pediatric patients and is reviewed elsewhere.1
TABLE five
Single Daily Dosing of Aminoglycosides in Adults with Dosing Interval Adapted for Creatinine Clearance*
| Drug | Dosage (mg per kg)† | CrCl: >60 mL per minute | CrCl: forty to 59 mL per minute | CrCl: 20 to 39 mL per infinitesimal | CrCl: <20 mL per infinitesimal |
|---|---|---|---|---|---|
| Amikacin (Amikin) | 15 | Every 24 hours | Every 36 hours | Every 48 hours | NR |
| Gentamicin | v to seven | Every 24 hours | Every 36 hours | Every 48 hours | NR |
| Netilmicin (Netromycin) | 5 to vii | Every 24 hours | Every 36 hours | Every 48 hours | NR |
| Tobramycin (Nebcin) | 5 to vii | Every 24 hours | Every 36 hours | Every 48 hours | NR |
TABLE half dozen
Values for Monitoring Aminoglycoside Serum Concentration Levels When Using the Single Daily Dosing Method of Administration*
| Drug | Serum concentration level for dosing every 24 hours (μg per mL) | Serum concentration level for dosing every 36 hours (μg per mL) | Serum concentration level for dosing every 48 hours (μg per mL) | Traditional method preferred (μg per mL) | Expected trough, before adjacent dose (μg per mL) |
|---|---|---|---|---|---|
| Amikacin (Amikin) | <8 | nine to 15 | 16 to 26 | >26 | <5.0 |
| Gentamicin† | <3 | 3 to 5 | 5 to 7 | >7 | <0.5 to 1.0 |
| Netilmicin (Netromycin)† | <three | 3 to 5 | 5 to 7 | >vii | <0.5 to 1.0 |
| Tobramycin (Nebcin)† | <3 | 3 to 5 | 5 to 7 | >vii | <0.5 to ane.0 |
TABLE vii
Traditional Multiple Daily Dosing of Aminoglycosides in Adults*
| Drug: road | Loading dose† (mg per kg) | Maintenance dose† (mg per kg) | Age: <sixty and CrCl: >90 mL per minute | Age: >lx or CrCl: 50 to xc mL per minute | CrCl: x to 50 mL per minute |
|---|---|---|---|---|---|
| Amikacin (Amikin): IV/IM | 7.5 | 7.five | Every 12 hours | Every 24 hours | Every 48 hours |
| Gentamicin: 4/IM | 2 to 3 | i.vii | Every 8 hours | Every 12 hours | Every 24 to 48 hours |
| Netilmicin (Netromycin): IV/IM | two to 3 | 1.7 | Every 8 hours | Every 12 hours | Every 24 to 48 hours |
| Tobramycin (Nebcin): IV/IM | 2 to 3 | 1.7 | Every 8 hours | Every 12 hours | Every 24 to 48 hours |
| Streptomycin: IM | vii.five | 7.5 | Every 12 hours | Every 24 hours | Every 48 hours |
TABLE 8
Desired Elevation and Trough Concentrations and Intervals for Creatinine Monitoring of Selected Aminoglycosides in Traditional Multiple Daily Dosing
| Drug | Peak concentration (μg per mL)* | Trough concentration (μg per mL)† | Serum creatinine |
|---|---|---|---|
| Amikacin (Amikin) | fifteen to 30 | 5 to x | Every 3 days |
| Gentamicin | 4 to 10 | <2 | Every three days |
| Netilmicin (Netromycin) | 4 to 10 | <2 | Every three days |
| Tobramycin (Nebcin) | 4 to x | <ii | Every iii days |
| Streptomycin | fifteen to 30 | v to x | Every 3 days |
TABLE 9
Aminoglycoside Regimens for Treatment of Endocarditis in Adults*
| Regimen | Trough concentration (μg per mL) |
|---|---|
| Streptococcal and enterococcal endocarditis | |
| Gentamicin, one mg per kg (upwards to fourscore mg) IV/IM every 8 hours | <2 |
| Streptomycin, 7.5 mg per kg (upward to 500 mg) IM every 12 hours | <5 |
| Staphylococcal endocarditis | |
| Gentamicin, ane mg per kg (up to 80 mg) Iv/IM every eight hours | <2 |
Table 10
Aminoglycoside Dosing in Infants and Children*
| Historic period | |||
|---|---|---|---|
| Drug: route | Cypher to seven days | Infants | Children |
| Amikacin (Amikin): Four | seven.5 to 10 mg per kg every 12 hours | 10 to 15 mg per kg every 12 hours | 7.v mg per kg every 12 hours |
| Gentamicin: IV | two.v mg per kg every 12 hours | ii.5 mg per kg every 8 hours | ii.v mg per kg every 8 hours |
| Netilmicin (Netromycin): Four | 2.5 mg per kg every 12 hours | 2.5 mg per kg every 8 hours | two.5 mg per kg every viii hours |
| Tobramycin (Nebcin): IV | two.five mg per kg every 12 hours | 2.v mg per kg every 8 hours | two.five mg per kg every 8 hours |
Cost
- Abstract
- Pharmacology
- Clinical Uses
- Drug Resistance
- Drug Interactions and Agin Effects
- Unmarried vs. Multiple Daily Doses
- Cost
- References
A comparison of the costs of single daily dosing and traditional multiple dosing should include not only the cost of the antibiotic but also the costs of labor, laboratory monitoring and drug toxicity. A pharmacoeconomic comparison of single daily dosing versus traditional dosing of gentamicin found a 54 percent reduction in drug supply and labor costs with single daily dosing. The aforementioned written report showed a 62 percent reduction in monitoring costs with single daily dosing.28 Since single daily dosing is often at least as effective (and may be less toxic and more cost effective), it may be the preferred method of administration in many clinical situations.
To see the total commodity, log in or buy admission.
REFERENCES
bear witness all references
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2. Montie T, Patamasucon P. Aminoglycosides: the complex trouble of antibody mechanisms and clinical applications [Editorial]. Eur J Clin Microbiol Infect Dis. 1995;14:85–7.
3. Edson RS, Terrell CL. The aminoglycosides. Mayo Clin Proc. 1991;66:1158–64.
iv. Chambers HF, Sande MA. The aminoglycosides. In: Hardman JG, Limbird LE, eds. Goodman and Gilman's The pharmacological basis of therapeutics. 9th ed. New York: McGraw-Loma, 1996;1103–21.
v. Lortholary O, Tod Thou, Cohen Y, Petitjean O. Aminoglycosides. Med Clin Northward Am. 1995;79:761–87.
6. Karlowsky JA, Zelenitsky SA, Zhanel GG. Aminoglycoside adaptive resistance. Pharmacotherapy. 1997;17:549–55.
7. Neu HC. The crisis in antibody resistance. Scientific discipline. 1992;257:1064–73.
8. Swartz MN. Use of antimicrobial agents and drug resistance. N Engl J Med. 1997;337:491–2.
ix. Tran Ba Huy P, Deffrennes D. Aminoglycoside ototoxicity: influence of dosage regimen on drug uptake and correlation betwixt membrane bounden and some clinical features. Acta Otolaryngol [Stockh]. 1988;105:511–15.
x. Choudhury D, Ahmed Z. Drug-induced nephrotoxicity. Med Clin North Am. 1997;81:705–17.
11. Hock R, Anderson RJ. Prevention of drug-induced nephrotoxicity in the intensive care unit of measurement. J Crit Care. 1995;ten:33–43.
12. Vogelman B, Craig WA. Kinetics of antimicrobial activity. J Pediatr. 1986;108(5 Pt 2):835–40.
13. Craig WA, Gundmundson Due south. Postantibiotic result. In: Lorian V, ed. Antibiotics in laboratory medicine. 3d ed. Baltimore: Williams and Wilkins 1991:403–31.
fourteen. Gilbert DN. Once-daily aminoglycoside therapy. Antimicrob Agents Chemother. 1991;35:399–405.
xv. Prins JM, Weverling GJ, van Ketel RJ, Speelman P. Circadian variations in serum levels and the renal toxicity of aminoglycosides in patients. Clin Pharmacol Ther. 1997;62:106–eleven.
16. Marra F, Partovi Northward, Jewesson P. Aminoglycoside administration as a single daily dose. An improvement to current practice or a repeat of previous errors? Drugs. 1996;52:344–70.
17. Galloe AM, Graudal N, Christensen Hour, Kampmann JP. Aminoglycosides: unmarried or multiple daily dosing? A meta-analysis on efficacy and safety. Eur J Clin Pharmacol. 1995;48:39–43.
xviii. Hatala R, Dinh T, Melt DJ. Once-daily aminoglycoside dosing in immunocompetent adults: a meta-analysis. Ann Intern Med. 1996;124:717–25.
19. Ali MZ, Goetz MB. A meta-analysis of the relative efficacy and toxicity of single daily dosing versus multiple daily dosing of aminoglycosides. Clin Infect Dis. 1997;24:796–809.
twenty. Bailey TC, Little JR, Littenberg B, Reichley RM, Dunagan WC. A meta-assay of extended-interval dosing versus multiple daily dosing of aminoglycosides. Clin Infect Dis. 1997;24:786–95.
21. Hatala R, Dinh TT, Cook DJ. Single daily dosing of aminoglycosides in immunocompromised adults: a systematic review. Clin Infect Dis. 1997;24:810–5.
22. Freeman CD, Strayer AH. Mega-analysis of meta-analysis: an examination of meta-assay with an emphasis on once-daily aminoglycoside comparative trials. Pharmacotherapy. 1996;16:1093–102.
23. Ferriols-Lisart R, Alos-Alminana 1000. Effectiveness and safety of once-daily aminoglycosides: a meta-assay. Am J Health Syst Pharm. 1996;53:1141–50.
24. Deamer RL, Dial LK. The evolution of aminoglycoside therapy: a single daily dose. Am Fam Physician. 1996;53:1782–6.
25. Thomson AH, Duncan N, Silverstein B, Alcock S, Jodrell D. Antimicrobial exercise. Development of guidelines for gentamicin dosing. J Antimicrob Chemother. 1996;38:885–93.
26. Drug facts and comparisons. St. Louis, Mo.: Wolters Kluwer, 1998:3673.
27. Bansal RC. Infective endocarditis. Med Clin North Am. 1995;79:1205–40.
28. Hitt CM, Klepser ME, Nightingale CH, Quintiliani R, Nicolau DP. Pharmacoeconomic impact of once-daily aminoglycoside administration. Pharmacotherapy. 1997;17:810–4.
Richard Westward. Sloan, One thousand.D., R.PH., coordinator of this serial, is chairman and residency program director of the Department of Family Medicine at York (Pa.) Hospital and clinical associate professor in family unit and community medicine at the Milton S. Hershey Medical Center, Pennsylvania Land University, Hershey, Pa.
Copyright © 1998 by the American Academy of Family Physicians.
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