New uses for older antibiotics

The combination of increasing resistance among selected gram-positive and gram-negative pathogens has prompted a re-evaluation of the antibiotic armamentarium, because few antimicrobials are effective against previously or newly highly resistant micro-organisms. Among the tetracyclines, doxycy-cline and minocycline maintain their effectiveness in their traditional areas of use (eg, rickettsial infections, ehrlichiosis, Lyme and other spirochetal infections) and against bacterial zoonoses [1,3]. In addition, doxycycline has been useful in treating community-acquired pneumonia, including PRSP strains; as prophylaxis or therapy for chloroquine-resistant P falciparum malaria; and for treating natural or bioterrorist anthrax or plague. Minocycline has been an effective antistaphylococcal antibiotic. Minocycline has potent anti-S aureus activity and is clinically effective against both MSSA and MRSA. Aside from linezolid, minocycline is the only oral antibiotic preparation that has been shown to be clinically effective against MRSA [2,8].

Among the aminoglycosides, amikacin has a structure that renders it resistant to inactivation by aminoglycoside-inactivating enzymes. In the past, amikacin has been used to treat gram-negative bacillary infections, and it remains the aminoglycoside with the greatest degree of anti-P aerugi-nosa activity. At the present time, amikacin is being used more than ever as part of combination therapy for additive or synergistic effect against highly resistant strains of P aeruginosa and Acinetobacter baumannii [1,9,10].

Nitrofurantoin has long been used primarily to treat asymptomatic bac-teriuria in pregnancy and to treat nosocomial urinary tract infections (ie, catheter-associated bacteriuria). Nitrofurantoin is active against all entero-coccal isolates and gram-negative pathogens except Proteus species and P aeruginosa. It is not commonly appreciated that nitrofurantoin is highly active against both VSE and VRE strains. In hospitalized patients who have catheter-associated bacteriuria, which is most commonly due to either Escherichia coli or enterococci (VSE or VRE), the use of nitrofurantoin over the years has not diminished its effectiveness against VSE and VRE lower urinary tract infections. Nitrofurantoin has re-emerged as the preferred oral agent to treat cystitis or catheter-associated bacteriuria due to VSE/VRE [2,11,12].

Colistin and polymyxin B are antibiotics that were introduced in the 1950s and were highly effective against strains of P aeruginosa. From a pharmacoki-netic perspective, polymyxin B and colistin were not studied extensively after their introduction, and they were believed to be highly nephrotoxic. Because of their unique detergent action on the cell membrane, there is virtually no acquired resistance to either colistin or polymyxin B in P aeruginosa or A bau-mannii. Proteus species are naturally resistant to colistin and polymyxin B. Because of the increase in multidrug-resistant (MDR) A baumannii and P aer-uginosa strains, these antibiotics are often the only agents effective against those highly resistant pathogens [13,14]. It is now recognized that colistin and polymyxin B have minimal nephrotoxic potential when administered properly. As the pharmacokinetic and pharmacodynamic properties of these antibiotics are further delineated, dosing will be optimized in the treatment of P aeruginosa or A baumannii bloodstream infections, central nervous system infections, and nosocomial pneumonia [15,16].


Nitrofurantoin is an oral antibiotic used to treat lower urinary tract infections. Nitrofurantoin does not concentrate in the upper urinary tract and is only available for oral administration. It has been used to treat asymptomatic bacteria in pregnancy because it does not cross the placenta. Nitrofurantoin concentrates in the lower urinary tract. It is active against the most common uropathogens causing nosocomial catheter-associated bacteria (ie, E coli and enterococci). Nitrofurantoin is active against all gram-negative aerobic bacilli causing urinary tract infections, excluding Proteus species and P aeruginosa. The adverse effects of nitrofurantoin are both acute and chronic and are uncommon and overemphasized [12,17].

Nitrofurantoin is being used increasingly at present to treat VRE nosocomial urinary tract infections (ie, catheter-associated bacteria). It is one of the few non-ampicillin derivatives that is active against enterococci. Ni-trofurantoin is active against both VSE and VRE. It is the preferred oral antibiotic for nosocomial VSE or VRE catheter-associated bacteriuria.

Prolonged and extensive use of nitrofurantoin over the past 50 years has not resulted in any resistance. Interestingly, its re-emergence as an important antibiotic in the therapeutic armamentarium is secondary to the increasing prevalence of VRE resulting from overuse of "high-resistance-potential" antibiotics (eg, intravenous vancomycin) (Box 1) [7,15,18-20].

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