The development and dissemination of antimicrobial-resistant pathogens in hospitals are major concerns. As mentioned earlier, is susceptible to efflux-mediated resistance mechanisms by S. pneumoniae, which can lead to the development of high-level resistance to fluoroquinolones as a class.
Ciprofloxacin are also susceptible to efflux mechanisms in E. coli, an important pathogen in genitourinary infections. Efflux mechanisms actively pump the antimicrobial agent out of the bacterial cell and thus lower the effective concentration of the drug, decreasing bacterial susceptibility and increasing the risk of resistance in the presence of subtherapeu-tic drug concentrations. It is not recognized by E. coli efflux pumps.
It is also important to consider the collateral damage associated with a therapy or class of antimicrobials. Much attention has been given lately to the growing number of cases of Clostridium difficile-associated diarrhea (CDAD) and methicillin-resistant Staphylococcus aureus (MRSA) in hospitals.
The difficulties associated with treating patients with potentially life-threatening infections such as CDAD and MRSA highlight the need for effective infection control measures to limit the spread of these organisms among hospitalized patients.
C. difficile-Associated Diarrhea Infection
CDAD is associated with the antimicrobial spectrum of an antibiotic, particularly its anaerobic activity and penetration to the intestines. This infection occurs via the outgrowth of C. difficile following antibiotic perturbation of the intestinal normal flora.
CDAD can more than double the three-month mortality rate of hospitalized patients and can significantly affect hospital costs because of the increased length of stay (nearly $3,700 per case in additional costs). As such, reducing the number of CDAD cases should remain a priority to limit costs and to optimize clinical outcomes.
Several reports have associated the use of fluoroquinolones, as well as other antimicrobial classes, as a risk factor for CDAD. Whether there are differences in the degree of these associations within members of the fluoroquinolone class is still under active debate.
For example, one case-control analysis attempted to assess the CDAD risk associated with fluoroquinolone use. It was found that ciprofloxacin and moxifloxacin were independently associated with the development of CDAD in hospitalized patients, whereas levofloxacin was not. Furthermore, in vitro and animal model studies have indicated that moxifloxacin can disrupt the colonic flora to a greater extent than levofloxacin and ciprofloxacin tablet. This may be attributed to the agent’s anaerobic activity and to the larger amount of active drug that passes through the GI system.
In contrast to the case-control study mentioned, a chart review of patients in a long-term-care facility indicated that levofloxacin canadian was associated with eight of nine cases of CDAD. These reports highlight the currently conflicting opinions about the roles of various fluoroquinolones in the development of CDAD.
Methicillin-Resistant S. aureus Infection
The rate of MRSA infections in hospital intensive-care units has reached more than 50%, and antimicrobial usage is a major risk factor. MRSA infections are very difficult to treat, because S. aureus exhibits resistance to multiple drugs, including the fluoroquinolones.
Thus, the fluoroquinolones are not indicated for MRSA infections, and fluoroquinolone usage in hospitals has been associated with a rising prevalence of MRSA. However, most studies group all agents in the fluoroquinolone class and do not differentiate among the specific effects associated with the individual fluoroquinolones. In vitro evidence suggests that differences may exist between agents in achieving PK/PD targets that prevent the emergence of S. aureus resistance. However, a correlation between in vitro data and clinical effects has not been established. Additional research is needed to fully assess the potential effects of the individual fluoroquinolones with MRSA rates.