Fluoroquinolone resistance

Empiric antibiotic therapy is an appropriate approach to traveler s diarrhea. Eradication of the causal microbe depends on the etiologic agent and its antibiotic sensitivity. Most cases of traveler s diarrhea and other community-acquired infections result from enterotoxigenic (ETEC) or enteropathogenic (EPEC) Escherichia coli. Routine stool cultures do not identify these strains primary empiric antibiotic choices include fluoroquinolones such as ciprofloxacin or levofloxacin. Azithromycin may be a feasible option when fluoroquinolone resistance is encountered. 

Until a few years ago, fluoroquinolones were the drug of choice for campylobacteriosis. However, a major problem among Campylobacter strains is growing resistance, occurring worldwide. Fluoroquinolone resistance in human isolates of C. jejuni in the United States occurs at a rate of 18%, and resistance levels in Barcelona and Thailand are over 80%. Fluoroquinolones should not be used unless susceptibility is confirmed. 

Although not reviewed in detail here, C. jejuni and C. coli are another major cause of inflammatory colitis that may be complicated by Guillain-Barre syndrome or reactive arthritis. In addition, their resistance to antimicrobials (particularly to quinolones) is increasing. In the United States, fluoroquinolone resistance of C. jejuni rose from 13% in 1997 to 18% in 1999 [112],... 

More recently, eveminomycins have also been introduced as antibiotics that inhibit the synthesis of bacterial cell walls. They show excellent activity against fluoroquinolone-resistant bacteria and all gram-positive vancomycin-resistant bacteria (Lin et al., 2000). 

Following the use of fluoroquinolones by the poultry industry, there has been a dramatic rise in the prevalence of the fluoroquinolone-resistant Campylobacter jejuni isolated in poultry muscle and liver, and in infected humans (34). Prior to the use of fluoroquinolones in poultry, no resistant strains were reported in individuals with no previous exposure to these drugs. In the past, some studies based on molecular markers showed a link between human and animal isolates of susceptible Campylobacter. Similar links of fluoroquinolone-resistant strains of Campylobacter jejuni with therapeutic failures in humans have recently been confirmed (34). 

The effect of fluoroquinolone-resistance in Campylobacter on the clinical outcome of treatment with a fluoroquinolone is not yet clear. There are conflicting data on whether resistant Campylobacter can cause more severe disease. Although there has been little documented impact of this resistance on human health, current concern about the potential human health consequences if resistance were to increase and spread, is high. Tims, further research and data-gathering are essential to quantify this potential. In addition to quinolone resistance, coresistance... 

Chen FJ, Lo HJ. Molecular mechanisms of fluoroquinolone resistance. J Microbiol Immunol Infect. 2003 36 1-9. 

WV Kern, M Oethinger, AS Jellen-Ritter, SB Levy. Non-target gene mutations in the development of fluoroquinolone resistance in Escherichia coli. Antimicrob Agents Chemother 44 814-820, 2000. 

LJ Piddock. Mechanisms of fluoroquinolone resistance an update 1994-1998. Drugs 58 Suppl 2 11-18, 1999. 

Food and Drug Administration-Center for Veterinary Medicine. 2000, October 18 (revised January 5, 2001). The Human Health Impact of Fluoroquinolone Resistant Campylobacter Attributed to the Consumption of Chicken. http //www.fda.gov/cvm/Documents/ RevisedRA.pdf (accessed June 16, 2006). 

Hwang DG. Fluoroquinolone resistance in ophthalmology and the potential role for newer ophthalmic fluoroquinolones. Surv. Ophthalmol, 2004, 49 (Suppl. 2), S79-S83. 

The inducible mar locus specifies a novel antibacterial mechanism that could well play an important role in the clinical emergence of fluoroquinolone-resistant E. coli isolates [274]. The mar regulon is one of several Mdr systems present in members of the Enterobacteriaceae [71]. Other Mdr systems include ... 

Goldstein MH, Kowalski RP, Gordon Yf. Emerging fluoroquinolone resistance in bacterial keratitis a 5-year review. Ophthalmology 1999 106 1313-1318. 

Zhang, Q. Lin, J. Pereira, S. Fluoroquinolone-resistant Campylobacter in animal reservoirs dynamics of development, resistance mechanisms and ecological fitness. Anim. Health Res. Rev. 2003, 4,... 

Fluoroquinolones must penetrate bacteria to reach their target, DNA gyrase. The second mechanism of fluoroquinolone resistance is decreased cell wall permeability. The fluoroquinolones diffuse through porin channels in the outer membrane of Gram-negative bacteria. Mutation results in a decrease in porin channel proteins, resulting in decreased uptake of the fluoroquinolones into bacterial cells. Alterations in a wide range of outer membrane proteins in Pseudomonas spp. result in resistance. From these mutations, the increase in MIC of the fluoroquinolones is relatively low (2-to 32-fold). Flowever, there is cross-resistance with unrelated antibiotics, most frequently cefoxitin, chloramphenicol, trimethoprim and tetracycline. 

Kaatz, G.W, Seo, S.M., and Ruble, C.A. (1993) Efflux-mediated fluoroquinolone resistance in Staphylococcus aureus. Antimicrobial Agents and Chemotherapy, 37 (5), 1086-1094. 

Marrer, E., Schad, K, Satoh, A.T, Page, M.G., Johnson, M.M., and Piddock, L.J. (2006) Involvement of the putative ATP-dependent efflux proteins PatA and PatB in fluoroquinolone resistance of a multidrug-resistant mutant of Streptococcus pneumoniae. Antimicrobial Agents and Chemotherapy, 50 (2), 685-693. 

Cill, M.J., Brenwald, N.P., and Wise, R. (1999) Identification of an efflux piunp gene, pmrA, associated with fluoroquinolone resistance in Streptococcus pneumoniae. Antimicrobial Agents and Chemotherapy. 43 (1), 187-189. 

C. jejuni is susceptible to a wide variety of antimicrobial agents. Fluoroquinolone resistance has increased to 10% to 13%... 

Target alteration. This can include mutation of the natural target (e.g., fluoroquinolone resistance), target modification (e.g., tibosomal protection from macrolides and tetracyclines), or acquisition of a resistant form of the susceptible target (e.g., staphylococcal resistance to methicillin caused by production of a low-affinity variant of penicillin-binding protein). 

No quinolone-inactivating mechanisms have been identified. Resistance has increased, especially in Pseudomonas and staphylococci. Fluoroquinolone resistance also is increasing in C. jejuni, Salmonella, Neisseria gonorrhoeae, and S. pneumoniae. 

Susceptibility factors Children The evidence for quinolone-induced arthropathy in children has been reviewed [33 ]. Data from animal studies and case reports, including tendon-related adverse reactions seen in adults, support a policy of restricting the use of fluoroquinolones in children and adolescents. The emergence of fluoroquinolone-resistant pneumococci is another reason for restricting their use. The authors cited statements from the American Academy of Pediatrics on cases in which... 

Neyfakh AA, Borsch CM, Kaatz GW (1993) Fluoroquinolone resistance protein NorA of Staphylococcus aureus is a mirltidrug efflux transporter. Antimicrob Agents Chemother... 

The improved uptake in fluoroquinolone-resistant isolates was correlated with the viscosity of hydrogels. The performance of hydrogels seems to be related to... 

The issue, however, is real because it was considered of such magnitude that the US Food and Drug Administration banned the use of the fluoroquinolone, enrofloxacin, for use in poultry in 2006 because of the supposed links with fluoroquinolone resistance in Campylobacter jejuni infections in man. It is interesting to note that this ban seemingly has had no effect on fluoroquinolone resistance in Campylobacter jejuni isolated from human cases of infection nor from isolates from chickens, as detailed by the NARMS 2009 Executive Report (Table 17.1). ... 

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