Resistant 'Superbugs' Create Need for Novel Antibiotics

Teri Capriotti, DO, MSN, CRNP


Dermatology Nursing. 2007;19(1):65-70. 

In This Article

Antibiotics Developed to Combat DRSP

Linezolid (ZyvoxAE), an oxazolidinone, is an antibiotic specifically developed for resistant bacterial infections. Linezolid interferes with bacterial protein synthesis at the ribosome. However, it is only bacteriostatic for staphylococcus and enterococcus. Investigators have found it has bactericidal activity against DRSP, and gram-negative and anaerobic bacterial infections (Anderegg, Sader, Fritsche, Ross, & Jones, 2005; Medical Ec onomics, 2005). Line zolid is recommended for pneumonia caused by drug-resistant strep tococcus pneumoniae, complicated skin and soft tissue infections, and diabetic foot infections. Available in oral and parenteral forms, it can be taken with or without food. Possible adverse effects include myelosuppression, pseu do mem branous colitis, and lactic acidosis. Also some drug-drug interactions are particularly significant.

Repeated studies have shown that linezolid is superior to vancomycin in treating MRSA infections, particularly ventilator-associated pneumonia and surgical site infections (Conte, Golden, & Kipps, 2002; Weigelt et al., 2005; Wunderink, Cammarata, Oli phant, & Kollef, 2003). Linezolid has out-performed glycopeptides in both HA-MRSA and CA-MRSA infections. Unfortunately, increasing reports of resistance and treatment failures have been associated with linezolid since 2005 (Shah, 2005).

Telithromycin (KetekAE ) is a ketolide antibiotic which blocks bacterial protein synthesis. Structural derivatives of macrolide antibiotics, ketolides are erythromycin-type drugs. Telithro mycin has been designed uniquely to combat DRSP. It is indicated for treating upper and lower respiratory infections, such as acute sinusitis, chronic bronchitis, and community-acquired pneumonia (Medical Economics, 2005). Strep tococcus pneumoniae, haemo philus influenzae, streptococcus pyogenes, and moxarella cat arrhalis are susceptible to tel ithromycin. It also is active against some of the atypical respiratory pathogens such as chlamydia pneumoniae, legionella pneumophila, and mycoplasma pneumoniae (Skerret & Stratton, 2004). However, it does not cover MRSA, GRE, or any enteric gram-negative bacteria (Shah, 2005).

Telithromycin is available as an oral agent and can be taken without regard for meals. Total recommended dosage is 800 mg per day administered as 400 mg in the morning and evening. It is well absorbed and penetrates respiratory tissues rapidly. An 800 mg daily dose is recommended for 5 days for chronic bronchitis or sinusitis. For community-acquired pneumonia, 800 mg should be administered daily for 7-10 days (Aventis Pharma ceuticals, 2004).

Because telithromycin is metabolized mainly by the liver, dosage adjustment may be necessary in patients with liver impairment. Caution must be used when telithromycin is co-administered with other hepatically metabolized drugs. Hepatic dysfunction can occur and may become apparent by elevated liver enzymes, hepatitis, or jaundice. Particular attention is needed when ketoconazole (NizoralAE), itraconazole (SporanoxAE), anti-lipidemic stat ins, midazolam (VersedAE), and cisapride (PropulsidAE) are administered concomitantly with tel ithromycin because these drugs have direct hepatic effects. Concomitant administration of rifampin (RifadinAE) should be avoided. Phenobarbital (BarbitaAE, SolfotonAE, LuminalAE), phenytoin (DilantinAE), and carbamazepine (TegretolAE) will cause sub-therapeutic levels of telithromycin. Digitalis (DigoxinAE), theophylline (TheolairAE, TheodurAE, Bronk odylAE, Slo-bidAE), metaprolol (Lo pressorAE, ToprolAE), and oral contraceptive levels may be affected by telithromycin.

Prolongation of the QT interval on the electrocardiogram has been observed in patients on teli thromycin. This can increase risk of ventricular arrhythmias. Therefore, patients with risk of cardiac dysrhythmia, bradycardia, or potential for hypokalemia or hypomagnesemia should not take telithromycin. It also is contraindicated in patients with myasthenia gravis (Medical Economics, 2005).

The most common side effects reported are diarrhea, nausea, vomiting, headache, dizziness, and persistent unpleasant taste. Antibiotic-associated pseu do membranous colitis due to clostridium overgrowth in the bowel is a potential side effect of all potent antibiotics. This condition should be considered in all patients with persistent diarrhea. Transient vision disturbances, such as blurriness and diplopia, also have been reported, usually after the first or second dose. A problem with focusing from near to far has been described as a side effect by some recipients of telithromycin. Visual disturbances prohibit the patient from driving, operating machinery, or engaging in any potentially hazardous activity. Also, this drug should be used with caution in pregnant or nursing women only if benefit outweighs risks. The drug's safety has not been investigated thoroughly in children. Dosage of teli thromycin has not been established for patients with severe renal impairment (Aventis Phar maceuticals, 2004; Medical Economics, 2005).

Ceftobiprole medocaril is an injectable anti-MRSA cephalo sporin antibiotic in development. Cephalo sporins are related closely to penicillins and act by destroying the bacterial cell wall. This new cephalosporin is in phase III clinical trials for complicated skin and soft tissue infections as well as nosocomial pneumonia caused by resistant strains of MRSA, enterococci, and S. pneumoniae. The Ceftobiprole in Hospital-acquired Pulmonary In fections (CHOPIN) study is a randomized controlled trial which began in 2005. It is focusing on patients who develop ventilator-associated pneumonia (Basilea Pharma ceutica J & JPRD, 2005).


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