___________________________________________________________________________ Antibiotics Review
THE OTHER BETA-LACTAMS (Continued)
Monobactams Aztreonam
IV: 1–2 g every 8 to 12 hrs
>9 mos: 30–50 mg/ kg/dose every 6 to 8 hrs Max: 120 mg/kg/day >7 years of age (nebulizer): Same as adult dosing
IV, IM, oral inhalation
Rash, nausea, vomiting, phlebitis at infusion site
Rare cross-sensitivity with allergy to other beta-lactams.
For oral inhalation, pretreatment with a bronchodilator is recommended.
Nebulizer: 75 mg 3 times/day at least 4 hours apart for 28 days; do not repeat for 28 days after completion.
Prescribing information is given for comparison purposes only. The higher dosage ranges reflect dosages for more severe infections. Please consult the manufacturer’s package insert for the antibiotic for complete prescribing information, maximum dosages, and indications. CNS = central nervous system; LFTs = liver function tests (liver enzymes). Source: [6; 16] Table 3
The binding site for aminoglycosides on the rRNA of the ribosome may also be altered, reducing binding. In addition, mutations that cause reduced uptake of aminoglycosides have been documented [81]. To combat resistances and overcome the relative natural resis- tance of enterococcus, other agents that target the cell wall are often used in conjunction with the aminoglycosides. Damage to the cell wall from the additional agents may be bactericidal in some cases and makes the cell wall more permeable to the aminoglycosides [82]. PHARMACOKINETICS The aminoglycosides are effective for the treatment of aerobic gram-negative bacilli, such as Klebsiella species, Enterobacter , and P. aeruginosa . There is very little activity against anaerobes and gram-positive organisms, so combination therapy with a beta-lactam, vancomycin, or other agents active against gram- positive organisms and anaerobes is commonly used. The ami- noglycosides are indicated for infections caused by susceptible organisms of the urinary tract, respiratory tract, skin and soft tissues, and sepsis due to gram-negative aerobic bacilli. The aminoglycosides commonly used at present for treatment of systemic bacterial infection include gentamicin, tobramycin, and amikacin. Kanamycin is discontinued [17]. Aminoglyco- sides have negligible oral absorption and thus require paren- teral administration. They also can be administered directly into body cavities and have a role in the management of pleural and peritoneal infection. Tobramycin is particularly useful for treatment of recurrent Pseudomonas infection in patients with cystic fibrosis and can be administered by aerosolized inhala- tion to facilitate optimal local antimicrobial effect [79]. In a large randomized, placebo-controlled clinical trial involving critically ill adults who had undergone invasive mechanical ventilation, a three-day prophylactic regimen of inhaled amika-
AMINOGLYCOSIDES The first aminoglycoside, streptomycin, was derived from Streptomyces griseus during the 1940s. Actinomycetes were studied for possible antimicrobial byproducts, and it was found that Micromonospora and Streptomyces produced useful agents. As newer, safer, and more effective aminoglycosides have been developed, the use of streptomycin is now confined primarily to certain management strategies for the treatment of tuberculosis. MECHANISM OF ACTION The basic structure of the aminoglycosides is an aminocyclitol ring. Different members of the family have different glycosidic linkages and side groups. The aminoglycosides have at least two effects on the bacterial cell that ultimately result in cell death. These agents bind nega- tive charges in the outer phospholipid membrane, displacing the cations that link the phospholipids together. This leads to disruption in the wall and leakage of cell contents. In addition, they inhibit protein synthesis by binding to the 30S subunit of the ribosome, causing miscoding and termination [80]. Although resistance to aminoglycosides is less common than with many other antibiotics, it can develop as a result of three known mechanisms. The most common pattern of resistance involves modification of the aminoglycoside molecule itself by enzymes produced by some bacteria. After the aminogly- coside is altered, it cannot bind as well to the ribosomes. The genes that encode for these enzymes are carried on plasmids, allowing rapid transfer of resistance between bacteria. Of note, amikacin has an S-4 amino 2-hydroxybutyryl (AHB) side chain that protects it against deactivation by many bacte- rial enzymes and is therefore less susceptible to this bacterial defense mechanism [81].
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MDTX2026
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