Resistant 'Superbugs' Create Need for Novel Antibiotics

Teri Capriotti, DO, MSN, CRNP


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

In This Article

Newer Antibiotics with Promise For MRSA, VRSA, and VRE

Second generation glycopeptides: Dalbavancin and Orita vancin

With the first generation glycopeptides (vancomycin and teicoplanin) as prototypes, the second generation glycopeptides have been synthesized. Dalba vancin and oritavancin have shown bactericidal activity against MRSA, VRSA, VRE, and DRSP and are undergoing the final stages of clinical trials (Bradley, 2005; Hoffman-Roberts et al., 2005; Van Bambeke, Van Laetham, Cour valin, & Tulkens, 2004).

In clinical trials, dalbavancin has shown efficacy against ser ious gram-positive hospital infections, particularly MRSA and teicoplanin-resistant strains. Due to the drug's long half-life of 9-12 days, a dalbavancin treatment regimen consists of a once-a-week intravenous dose. The pharmacokinetics of this drug allow an intermittent dosing schedule which could be suitable for home intravenous therapy. A once-a-week dose schedule could obviate the need for continuous intravenous lines and decrease risk of iatrogenic local or bloodstream infections (Mushtaq, Warner, Johnson, & Livermore, 2004).

Oritavancin, like dalbavancin, is under investigation in the late phases of clinical trials. It ex hibits potent antimicrobial activity against vancomycin-resistant sta phylococcus aureus and enterococcus species. It has a long half-life of approximately 6-10 days, allowing for an infrequent dosing schedule. Oritavancin has dem onstrated efficacy in the treatment of complicated skin and soft tissue infections (Coyle & Rybak, 2001). Few studies elucidate the side effects and tolerability of dalbavancin and oritavancin. When available for patient use, both these drugs should be limited to treatment of only multi-drug resistant gram-positive bacterial infections.

Daptomycin (CubicinAE)

This cyclic lipopeptide represents a new class of antibiotic. This drug exhibits concentration-dependent bactericidal activity against resistant gram-positive bacteria by inhibiting protein synthesis, and DNA and RNA synthesis. It is bactericidal against staphylococcus aureus including MRSA, staphylococcus epidermidis (in cluding methicillin-resistant S. epidermidis [MRSE]), enterococcus including VRE, penicillin-resistant S. pneumoniae, and S. pyogenes (also called group A beta hemo lytic streptococcus [GABHS]). Daptomycin has been effective for the treatment of skin and soft tissue infections. However, it has not shown efficacy in pneumonia (Hirsch, 2004).

The drug was approved by the Food and Drug Admin istration (FDA) in 2003 for intravenous administration only. Dap tomycin should be administered at a dosage of 4 mg/kg in 0.9% sodium chloride over a 30-minute period once every 24 hours for 7-14 days. It is not compatible with dextrose intravenous solutions. Eliminated primarily by the kidney, the drug should have dosage modification for patients with renal impairment. It has not been tested sufficiently in children, or pregnant or nursing women. Currently daptomycin is undergoing investigation for treatment of bacteremia and endocarditis (Pham, 2003).

Tigecycline (TygacilAE)

This is a broad-spectrum glycylcycline antibiotic similar to the tetracycline class of drugs. It has activity against a broad range of gram-positive, gram-negative, atypical, anaerobic, and antibiotic-resistant bacteria including MRSA, VRE, and PRSP. It is bacteriostatic against these organisms, not bactericidal. Tigecycline binds to bacterial ribosomes, inhibiting bacterial protein synthesis. It is most effective for complicated skin and soft tissue infections and intra-abdominal infections ac quired either in the hospital or the community (Smith, McCabe, & Aeschlimann, 2005).

Tigecycline was FDA app roved in 2005 for intravenous administration only ("FDA App roves," 2005). It should be administered as 100 mg for the first dose over 30-60 minutes followed by a 50-mg dose every 12 hours for 5-14 days. No dosage adjustment is needed in patients with renal or liver impairment. Tig ecycline may interact with warfarin and inactivate oral contraceptives; the patient on warfarin must be cautioned about possible bleeding, and patients using oral contraceptives require another method of birth control. The drug has not been tested adequately in children, or pregnant or nursing women. Similarly to tetracyclines, tigecycline may cause photosensitivity and gastrointestinal effects, such as nausea, vomiting, and diarrhea. Use in children will cause permanent discoloration of teeth. Pain and swelling at the injection site can occur (Nathwani, 2005).


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